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The biological applications of DNA nanomaterials: current challenges and future directions

Wenjuan Ma, Yuxi Zhan, Yuxin Zhang and 3 more

Signal Transduction and Targeted Therapy · 2021 · Review · CC BY

Abstract

DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With the rapid progress in DNA nanotechnology, multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson–Crick base-pairing for molecular self-assembly. Some DNA materials could functionally change cell biological behaviors, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNAs (ssDNAs) or RNAs with secondary structures via self-pairing, named aptamer, possess the ability of targeting, which are selected by systematic evolution of ligands by exponential enrichment (SELEX) and applied for tumor targeted diagnosis and treatment. Some DNA nanomaterials with three-dimensional (3D) nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic agents. While the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies, and also proved with great potential in the biological and medical use, there is still a long way to go for the eventual application of DNA materials in real life. Here in this review, we conducted a comprehensive survey of the structural development history of various DNA nanomaterials, introduced the principles of different DNA nanomaterials, summarized their biological applications in different fields, and discussed the current challenges and further directions that could help to achieve their applications in the future.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1DNA was used for the storage of genetic information as a common biomolecule and fundamental hereditary material in different creatures., DNA materials possess the potential for nanofabrication due to its characteristic nature, i.e., high precision of Watson–Crick base-pairing and high controllability.,– In 1980s, Seeman et al. proposed the rules for the synthesis of DNA nanostructures for the first time, which triggered a booming years of DNA nanotechnology development.– In the following decades, the technology of DNA nanostructures developed and improved rapidly, and various DNA nanostructures have been designed and widely applied as generic polymeric materials to form complex nanoparticles for specific usages in the fields of chemistry and biomaterial.–

2DNA, the carrier and transmitter of genetic information in all living systems, consists of four different deoxynucleotide monomers. Each monomer is formed with a phosphate group, a deoxyribose, and one of four nitrogen-involving nucleobases, while the nucleobases include thymine (T), adenine (A), guanine (G), and cytosine (C)., Between the monomers, the phosphate group and the deoxyribose can form the phosphodiester bond, which links a certain number of monomers into a DNA chain, named single-stranded DNA (ssDNA)., Based on the principle of Watson–Crick base-pairing, the continuous ssDNA can pair with another one in antiparallel directions to form a double-helix DNA structure, that is double-stranded DNA (dsDNA). Between the two polymeric chains, the nucleobases of C and G can form three hydrogen bonds, and A and T can form two hydrogen bonds, resulting in the base pairs with the certain complementary ssDNA inside the dsDNA.–

3Despite that DNA molecule is composed of simple units, the variety of dsDNA and the programmability of the structure can be realized by accurate design and freely defined constitutions. In artificially synthesized dsDNAs, the quantity and order of the four monomers are accurately arranged as designed, which determines the diversity of dsDNAs. The freely defined constitutions of DNA are based on sequence-specific base attacking interactions, which are determined by both the external conditions and the sequences of DNA duplexes.– With the rapid development of nanotechnologies and availability to manage the constructions of DNA nanostructures, a variety of designable principles and plentiful DNA-based rigid titles have been used to prepare various dimensional architectures into rationally assembling nanoparticle templates or biomolecular scaffolds,– such as tile assembly,, origami structure,– and dynamic nanomechanical system.– Owing to the inherent nature of biocompatibility and biodegradability of DNA material, different kinds of structural and functional materials based on DNA have been reported with promising potential for many biological usages in different fields.– Subsequently, DNA nanotechnology and nanomaterials kept gaining increasing interests in DNA material science and engineering, especially with the development of DNA nanotechnology triggering by the growing demands in biological, chemical, or medical-related usages.–

4DNA nanomaterials were developed with a wide variety of structures, including two- and three-dimension (2D and 3D) constructions. Furthermore, according to the various molecular building-styles of functional DNA materials, the constructions of artificially synthesized DNA nanostructures contain single-layer and multilayer nanostructures, which also can be sorted into linear, circular, and branched form. The DNA origami technique makes it easy for preparation of DNA, which also promotes the explosive development of structural DNA nanotechnology. The advanced development of DNA nanotechnology then breeds various novel DNA nanomaterials that are applied widely, including tissue engineering, immune engineering, drug delivering, disease diagnosis, and as tools for molecular biology or as biosensors.–,– However, for therapeutic applications, some multifunctional polymeric DNA nanomaterials still maintain drawbacks, including being easily-metabolized, lack of targeting, and instability.– Therefore, the combinations of DNA nanomaterials and other nanoparticles and hyper-polymeric compounds, such as gold nanoparticle (AuNPs),,, polyethylenimine (PEI),– chitosan,– and poly-l-lysine (PLL),– are also developed to overcome those limitations.

5While the structural DNA nanotechnology has developed quickly and proved important, the studies on the application of those DNA nanostructures are actually more practical and critical.,– In such efforts, some previous studies demonstrated that some DNA scaffolds with specific structures or other materials could affect cell biological behaviors, such as cell viability,, proliferation,,,, migration, differentiation,, morphology, and autophagy. Owing to the special nature, DNA-based materials could be employed in tissue regeneration engineering and potential treatments for some diseases.,– In this aspect, many DNA nanostructures were also combined with other materials, such as nucleic acid aptamer (DNA and RNA),– polypeptide,– protein,,– and some chemical drugs,– in which the DNA nanostructures were designed as delivery systems. When combined with nucleic acid aptamer, the complex DNA-based nanostructures could enhance the ability of targeting,,, inhibition of malignant cells, and antitumor effects.,, More complex designs of DNA origami enable more advanced applications in other fields, such as in photonics,– electronics,– reaction networks of artificial enzymes,, and etc. This review will summarize the structural design and self-assembly of DNA nanostructures and their biological applications, and discuss the current challenges and future directions.

Fundamentals of DNA origami design

6The structural DNA nanotechnology was pioneered by Ned Seeman and colleagues from 1982. There arouse an interest in DNA structures, which developed tremendously thereafter.– The DNA formed stabilized branch junctions, which can be further modified via sticky ends to form higher-order structures and lattices, is the vital foundation of structural DNA nanotechnology including DNA origami. As for the intrinsic internal sequence symmetry, the branched DNA structures are naturally mobile, and the sequence symmetry should be minimized to form stable branched junction., Seeman et al. suggested to possibly use the stale junction to synthesis 3D frameworks of nucleic acids via legitimately designed sticky-end associations. They assembled different multi-arm junctions, including 4-, 5-, 6-, 8-, and 12-arm junctions, demonstrating that DNA junctions could be precisely branched.– However, considering the structural flexibility and the unpredictable conformations, multi-arm junctions are not suitable to act as the basic structural elements, which are needed to assemble higher-order periodic lattice structures. To solve this problem, Seeman and colleagues constructed a DNA double-crossover molecule by creating a structural motif with two 4-way junctions, constructing a rigid DNA molecule by two crossovers., In 1990s, a periodic 2D crystalline, the first higher-order DNA lattice nanostructure, was successfully made from crossover molecule. In 2003, LaBean and colleagues added crossover molecule into a 4 × 4 DNA title with four different direction arms. The 4 × 4 DNA title has a long central strand to connect four Holliday junctions together into a rigid, branched, and fourfold symmetry, similaring to the crossover molecule with a central strand to link two Holliday junctions by end to end. The 4 × 4 title reduced the probability of stacking interactions between each arm by placing T4 loops at each of the four concerns of the central strand. Nanoribbon or 2D grid-like lattice was successfully synthesized via supporting 4 × 4 title with appropriate sticky end association sites. For the inspiration of the 4 × 4 title and crossover molecule, some DNA basic units, such as three- and six-point star title, and six-helix bundle, were successfully assembled.– These DNA basic units can further self-assemble to construct 2D arrays with various patterns. The 3D macroscopic crystal could also be successful synthesized by the assembly of a rationally designed tensegrity triangle motif.

7In addition to synthesizing periodic DNA nanostructures by titles, LaBan et al. also investigated a long scaffold to guide the nucleation of DNA titles into barcode DNA lattices with complicated aperiodic nanostructures. The long DNA scaffold consisted of shorter synthetic oligos, for adding binding sites to shorter strands and forming larger individual complex with barcode DNA nanostructures, which could be further constructed into latticed nanostructures if different sticky ends provided. Shih et al. constructed an octahedron using a ssDNA with 1.7 kilobases. Six four-way junctions at each vertex and five double-crossover struts were embedded into the octahedron structure. The synthesis of the octahedron structure includes two steps as follows: (1) five staples with 40 nt bind to the 1699-nt scaffold, assembling a giant branched molecule with bulges at different arms; (2) each arm associating with its partner by the paranemic cohesions interactions, forming the final octahedron-shaped nanostructure.

8The fundamental concepts of DNA nanotechnology and previous explorations established a solid foundation, facilitating greatly the development and the design of DNA nanostructures to be more convenient, complex, and diverse.

Single-layered DNA nanostructure designs

9The DNA origami technology was firstly reported by Paul Rothumend in 2006. The synthesis of some single-layered, complanate structures, whose structures ranged from triangular, simple rectangular and five-point star shape to intricate smiley faces, each with its unique size, ranges roughly 100 nm in diameter. The procedures related to the design and self-assembly process have been described in detail by Paul Rothumend et al. Since then, other studies were inspired and successfully synthesized 2D planar patterns, including a depiction of dolphins and a map of China., Then, the creation of complex curvatures within 2D planar patterns and 3D planar nanostructures were reported by Han et al. The distances of the consecutive crossovers, which can concatenate adjacent helices, are usually constant along the parallel alignment of DNA helices. Nevertheless, if the distance of the crossovers along the inner helices is less than that of outer helices, the tension could make the outer helices bend. This method was successfully adopted to incorporate DNA into concentric ring or square with rounded angels.

10Some previous studies reported the applications of two general strategies to investigate 3D nanostructures, and the 3D nanostructures were based on the single-layered design of double-crossover. The first strategy depends on a second-step folding to build 2D planar DNA nanostructures. However, some 2D planar DNA nanostructures are not completely paired with staples. The 2D planar DNA nanostructure is intentionally left as a single-strand at the certain parts so that some 2D planar DNA nanostructures could form some well-cut pieces, such as squares and triangles. When 2D shapes join in with the matched well-cut pieces, the 2D nanostructures could fold and transform into 3D shapes. For instance, a boxlike DNA nanostructure with the external size of 36 × 36 × 42 nm3 had a lid which opened and closed like a box. A 3D DNA box-shaped structure with a switchable lid was also reported, and the DNA boxlike nanostructure had a unique electron microscopy, which could potentially be used widely including delivering drugs, controlling the function of some single molecules, and molecule computing.– Other studies developed a stepwise folding mechanism that was self-assembled by a set of staples, to form a DNA prime and a cuboidal boxlike nanostructure.,

11The second strategy applying to develop 3D DNA nanostructure was used to introduce crossovers and to use plane linkages. The parallel DNA nanostructures did not form the single plane, such as DNA nanotubes. By using the approach with the in-plane curvature strategy, some tanglesome nanostructures including the 3D sphere, nanosized flask, and football were developed. The double-crossovers DNA nanostructures are relatively rigid structural motifs. However, when compared to duplex DNA at the large size (such as ~100 nm), the structures of single-layered DNA nanostructure are still flexible.

Wireframe single-layered designs

12Given that the designs were based on the double-crossover motifs, the wireframe single-layered DNA nanostructures that were conducted with different design strategies were formed by aligning DNA helices in the parallel and compact way. If some new motifs are added to the DNA nanostructure, new nanostructures will be achieved, such as multi-arm junctions allowing for the mash style of desired patterns. A square junction was used for creating branched nanostructures, which was connected with the stem of the branch region to only one of the base helices of the desired feature, and allowed to the connecting helix to remain at the right angle. The first wireframe DNA nanostructure with a gridiron pattern was created by Han et al. The gridiron pattern consisted of four 4-arm junctions, and they joined in each other to form a square frame. Connecting some gridiron patterns together with a consecutive strand could result in a series of 2D lattice DNA nanostructures. Subsequently, Zhang et al. studied another strategy to make much more intricate wireframe nanostructures with a number of multi-arm junctions. Based on the multi-arm junction, the design algorithm named DAEDALUS was created to fully automate the scaffold routing and staple assignment for some specific target DNA nanostructures.

13In addition, Benson et al. created a new DNA nanostructure with a more open conformation with one helix per edge. The structure is therefore stable under the ionic conditions that were always applied for biological assay. The structure was conducted arbitrary target objects to the triangulated meshes to create DNA nanostructures in a wireframe style by using an alternative way., A single DNA helix rather than two is the majority of the edge designs, which requires the DNA scaffold traveling through all of the edges at once, while a few edges require the DNA scaffold to travel twice. The novel multi-arm DNA structures combined with the DNA origami method for the synthesis of 2D DNA scaffolds with folding into 3D by connection strands on the 2D nanostructures, and the novel multi-arm DNA structures were designed with a scaffold routing whose fundamental structures were the A-trails to form the center of the nanostructures through a computational algorithm., The availability of this method was further demonstrated by means of the successful preparation of a series of meshed 3D nanostructures, such as ball, bottle and stanford bunny. The same design concept was also used to synthesize triangulated DNA origami trusses.

14Based on the design concept once adopted, many different approaches can be used to create single-layered DNA nanostructures. In spite of successful formation and high yield, several limitations remain when the DNA structures were used in practical applications. For instance, single-layered DNA nanostructures have structural heterogeneity and conformation, which might restrict the applications in precise addressability. Owing to the vertex discontinuity of the DNA chains, it is difficult to avoid the structural flexibility in the single-layered wireframe design. In addition, the technologies of single-layered DNA nanostructures also shows the potential of biochemical reactions at the single-molecule level.

Multilayered designs

15Single-layered DNA nanostructures could be aggregated to form multilayered 3D nanostructures with the increase of rigidity, which could overcome some limitations and improve the design methods. In the first study on designing 3D solid DNA nanostructures, the DNA nanostructures were based on a six-helix bundle as the fundamental unit. Douglas et al. demonstrated the design and self-assembly process of DNA nanostructures with six different shapes, including monolith, railed bridge, square nut, stacked cross, genie bottle, and slotted cross, and the dimensions with precise controlling ranged from 10 to 100 nm. Douglas et al. also reported the validity of the design method by assembling a monolith, square net, and slotted cross by using a honeycomb alignment. In another study, Ke et al. reported a new approach to design a multilayer DNA structure with a square lattice, which was based on a four-helix bundle. In this design, the square lattice could be folded into the nanostructures of designed dimensions by one-step annealing process, in spite of the intensive density of DNA helices. The three-helix bundle was regarded as the basic unit in a triangular lattice. In this study, Ke et al. reported the successful folding of a multilayer DNA structure with helices arranged on the close-packed hexagonal lattice. This study also presented that hybrid DNA structures could incorporate three different shapes all in one design, including square lattice, honeycomb-lattice, and hexagonal-lattice packing of helices.

16More work reported that the multilayered DNA nanostructures could be designed to incorporate more various packaging styles, which possess the programmable curvatures and twists. In this research, Dietz et al. systematically demonstrated that the strands of DNA with programable self-assembly could form a custom-shaped bundle of tightly cross-linked double helices, and they also created several different shapes of intricate DNA nanostructures via combining multiple curved elements together. Another method combined single-strand DNA flexibility and multilayered nanostructure rigidity to build the tensegrity structures. Tensegrity, also named tensional integrity, is a structural principle related to the usage of isolated component, indicating a reliable balance between components in pure compression or pure tension for stability. Liedl et al. successfully synthesized a tensegrity prism that was formed with three multilayered DNA bundle nanostructures as compression components and nine ssDNAs regions as tension cables.

17Ke et al. introduced that the multilayered DNA nanostructures had much better rigidity than that of the single-layered DNA nanostructures. Nevertheless, the longer folding course need to avoid the kinetic traps, and the buffer solution should contain a high concentration of magnesium (Mg2 + ), which could suppress the electrostatic repulsion of the negatively charged phosphate backbones between adjacent helices. Furthermore, due to the lower accessibility and shorter nucleation region of folding DNA strands, the yield of the single-layered DNA nanostructures is usually higher than that of the compact multilayered DNA nanostructures. The careful design of the scaffold procedure and staple break positions could boost the folding yield of DNA nanostructures. The parallel alignments of DNA nanostructures in a layer-by-layer fashion are not necessarily required for the 3D DNA nanostructures. Hong et al. reported a strategy to design a layered 3D wireframe DNA nanostructure by employing crossover pairs, which could connect neighboring layers of DNA double strands together. The layered crossovers could make the scaffold or helper DNA strands go through different layers and get command of the relative direction of DNA strands within the neighboring layers. In this research, the authors successfully created a nine-layered wireframe DNA nanostructure and reported that the neighboring helices could be controlled within well-defined interlayer angles. The 3D latticed nanostructures could also be constructed by applying 3D point-star junctions. However, it would be a challenge to availably control its relative direction in the interspace of 3D.

18The design methodologies of DNA nanostructures depend on the usage of DNA molecules rendering objects. An object can be generated by scientists via using of DNA origami or a 3D modeling software. With the adoptions of DNA origami and 3D modeling software, objects can be folded from the 2D plane, visualized as outlined meshes, or filled with layered lines. The preparation procedures of various DNA nanostructures are conducted under a good framework now: (1) composing an object nanostructure, (2) creating the scaffold style layout and defining the DNA sequence by using a software program,, (3) designing the oligoes of the scaffold and staple, (4) enabling DNA self-assembling under a buffer solution with the ramp of temperature, (5) purifying and functionalizing the DNA nanostructure when needed, (6) analyzing and visualizing the DNA nanostructure, and then (7) expanding and exploring the various applications of the DNA nanostructure.– Various methods have been created to improve the synthesis processes of DNA nanostructures, such as increasing the production efficiency of DNA nanostructures,– packaging the DNA nanostructures in a Mg2 + -free buffer solution with an isothermal environment,– and purifying the functionalized DNA nanostructures to wipe off any misfolding nanostructures or polymers.– Some other studies have also developed a few methods to apply DNA nanostructures into different experimental conditions, such as the application of photoinduced crosslinking with 8-methoxypsoralen (8-MOP), which could improve the heat resistance of the DNA nanostructures;, the application of external signal triggers such as magnetic or electric fields, chemical, light, pH, and temperature, which could control the formation of DNA nanostructures;– and the application of imaging and folding DNA nanostructures in hydrated glycholine under isothermal conditions.

Biological applications of various DNA nanostructures

19The final objects of various DNA nanomaterials are the application for different field, such as biomedicine, chemistry, materials, and etc. However, the structural development is way ahead of the applications of DNA nanomaterials. In this part, we will summarize the biological applications of different DNA and DNA-based materials, and discuss the challenges of them. The contents of this part are mainly devided into six small parts shown as follows.

Tissue engineering

20Tissue engineering is a cutting-edge field that study seeded cells, suitable physical and biochemical factors, and biocompatible materials, as well as combinations thereof, to promote the creation of tissue-like structures., Tissue engineering mainly involves cartilage and bone construction, vascular tissue engineering, nerve tissue engineering, skin tissue engineering,, oral tissue engineering, tendon and ligament tissue engineering, corneal tissue engineering, and tissue engineering of some other important organs (e.g., liver, pancreas, kidney, and lung)., The therapeutical strategies adopted mainly include seeding cells,– synthesizing biological materials,– constructing tissues and organs with advanced methods and techniques,– and clinical applications.,, At present, there are mainly three ways of tissue repairing commonly used in clinical practice: autologous tissue transplantation, allogeneic tissue transplantation, and artificial substitutes. For tissue regeneration engineering including cell seeding, proliferation, orientation, and differentiation of the stem or progenitor cells on the injured sites, various bio-mimicked materials or medicines with the use of nanotechnology were studied to provide the adhesive surfaces.– The nanotechnology can be used to develop and investigate different nanomaterials and medicines, which can provide different substrates for cell seeding, adhesion and growth, to aid the tissue regeneration on the defects.,,– The most important purpose of regenerative nanomaterials and medicines is to rebuild or create functional tissue replacements to repair the function and morphology of defected tissues. In this part of the review, we will summarize the applications of DNA nanostructures, discuss the limitations of different studies, and present the gap between the studies and clinical applications.

21With the rapid development of DNA nanotechnology, the applications of DNA nanostructures in tissue regeneration engineering are embodied in altering biological behaviors of cells, such as morphology, viability, growth, and migration., The potential applications of DNA nanostructures in tissue regeneration include the regeneration of bone and cartilage (Fig. 1g),,, nervous system (Fig. 1a, f),,, and integumentary system (Fig. 1b),– as well as changing the stress response of tissue, such as anti-inflammatory effects,, anti-aging effects, and anti-apoptosis (Fig. 1). Owing to the interesting feature of DNA with the ability to intercalate synthetic or natural molecules, such as daunorubicin, amsacrine, and adriamycin, the combinations of DNA nanostructures and other molecules are regarded as complex drug delivery systems (DDSs) for many active and photosensitive compounds (Table 1).– Therefore, the DNA-based nanostructures or nanomedicines are exerting their effects on tissue regeneration engineering.–

Bone tissue engineering

22The loss and dysfunction of bone tissue, which are mainly caused by aging, injury, inflammation, such as rheumatoid arthritis (RA) or osteoarthritis (OA), and tumors, are associated with individual susceptibility, and can result in severe morbidity and socio-economic issues., In the skeletal tissue, the DNA nanostructures are mainly used to provide the adhesive scaffolds or delivery some biological agents to the injured articulations, and the DNA nanostructures as the delivery system could overcome some drawbacks of other biological agents, such as poor penetration level and low stability.

23At the first decades, the main application of DNA nanostructures in bone tissue was gene therapy by using plasmid DNA (pDNA).,,– In previous studies, the pDNA or other DNA nanomaterials were usually designed as the delivery systems to transport some growth factors and genes, including fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and vascular endothelial growth factor (VEGF),– which was regarded as viral gene delivery (Fig. 1g). The combinations with different materials and seed cells were also conducted in a vast of studies, and the purpose was to promote the seed cell proliferation and differentiation into the functional target tissues including bone and cartilage.– The treatments based on different recombinant human growth factors have been investigated and the therapeutic effects were encouraging. Owing to the short half-lives of recombinant human growth factors and the needed for clinical effectiveness, supraphysiological dosages were used, and their production was expensive., The supraphysiological dosages of recombinant human growth factors could also cause several side effects, such as ectopic formation of bone tissue and soft tissue swelling. Therefore, the non-viral gene therapy then became a promising alternative strategy for bone tissue repair.–

24In studies within recent decade, the non-viral gene vectors were developed by combining DNA with other scaffolds.,– The complex of DNA and poly(lactic-co-glycolic acid) (PLGA)/HAp composite scaffolds was constructed to delivery pDNA-BMP-2 into bone marrow stem cells (BMSCs) and enhance the DNA transfection efficiency, which was quite encouraging and promising for bone regeneration.– Previous studies reported that the delivery of FGF-2 and BMP-2 genes could upregulate the transcription of Runx2 and osteocalcin,, and Salem et al. reported that non-viral gene delivery of FGF-2 and BMP-2 via pDNA could attenuate the harmful effects of diabetes mellitus on bone regeneration at the defect sites. PLGA was used to encapsulate the novel nanoparticles that consisted of polyethylenimine (PEI) and human pDNA-BMP-2 to create pBMP-2/PEI nanoparticles for bone formation., The BMP-7 and VEGF-A genes were encoded into the injectable DNA-loaded nano-calcium phosphate paste, and the nanocomplex was regarded as bioactive bone substitution material. The DNA-loaded bone paste encoding with BMP-7 and VEGF-A showed enhanced regeneration of bone volume and significantly faster healing in critical site of bone loss at the early stages. The DNA-loaded nanoparticles could release DNA, resulting in cell transfection, and then promote the expression of BMP and VEGF in bone cells. Takanche et al. found that pDNA-c-myb conjugated with chitosan-gold nanoparticles (Ch-GNPs/c-myb) could suppress osteoclastogenesis and promote osteogenesis of dental implant even in osteoporotic condition, making an applicable material to sustain dental implant integration and therapy in some degenerative bone diseases., Some studies loaded BMP-2 gens (pDNA-BMP-2) into a chitosan (CS)-based hydrogel with a,b-glycerophosphate (a,b-GP), termed CS/CSn(pDNA-BMP2)-GP. The CS/CSn(pDNA-BMP2)-GP then possessed excellent capability in enhancing cell proliferation, maintaining great potential in gene delivery system and tissue regeneration of periodontium.– Chitosan/β-glycerophosphate (CS/β-GP) hydrogel as a VEGF-sustained release system could delivery and release VEGF, and promote cell proliferation and differentiation of dental pulp stem cells (DPSCs). Huang et al. applied lipopolysaccharide-amine nanopolymersomes (LNPs) to delivery Noggin small interfering (si)RNA (siNoggin) and pDNA-BMP-2 to transfect cells, respectively. This study demonstrated that LNPs/siNoggin and LNPs/pBMP-2 could both enhance the osteogenic differentiation, and the osteogenic differentiation of LNPs/siNoggin was better than that in LNPs/pBMP-2. Moreover, different structural variations of star-shaped poly(l-lysine) polypeptides were used as promising nano-viral gene delivery systems for mesenchymal stem cells (MSCs), which could irritate MSCs to differentiate into bone tissue by delivering pDNA-VEGF and pDNA-BMP-2. Novel DNA/protamine complex scaffold was developed for a number of clinical usages, such as enhancement of bone regeneration,, and pasting and delivery the genes of pDNA-FGF-2 or pDNA-BMP-2.,

25Beyond the application of pDNA in bone tissue regeneration, some other DNA nanostructures were also developed for bone regeneration with their own features in recent decades. Some functional DNA materials were synthesized to promote the reconstruction of bone tissue, and some DNA materials could deliver drug monomers to exert anti-osteoarthritis effects. Tetrahedral DNA nanostructures (TDNs) have the specific framework and can be internalized by different cells, in which they can change the cell biological behaviors (Fig. 1g). Lin et al. reported that TDNs could enhance the cell growth and motility of different cells, such as adipose stem cells (ASCs), human periodontal ligament stem cells (PDLSCs), MSCs, and chondrocytes.,,– TDNs could also induce stem cells toward osteogenic differentiation., Zhou et al. also reported that the TDNs could act the anti-inflammatory effects on the periodeontitis model, and could promote osteogenic differentiation. In this study, the TDNs acted the effects of anti-inflammations and regeneration on bone tissue, and the results suggested that DNA nanomaterials might be applied for some inflammatory diseases. In a recent study, TDNs were employed as the delivery loaded with Wogonin to form the TDNs/Wogonin complexes. The TDNs/Wogonin complexes were verified as a potential nanomedicine for osteoarthritis by executing different biological effects, including enhancing expression of chondrogenic markers, downregulating matrix metalloproteinases and inflammatory mediators, and promoting the expression of tissue inhibitor of metalloproteinase 1 and B-cell lymphoma 2. The TDNs/Wogonin thus proved itself with great potential as an injectable nanomedicine in the treatment of osteoarthritis.

26The DNA materials applied for bone regeneration were mainly the combinations of pDNA and other materials for enhancing the gene transfection efficiency to turn gene on or off, and the pDNA used was usually adenovirus plasmid., In general, for the easy laboratory manipulation, considering the features of porosity, adjustable degradation rate, and good mechanical property of natural and synthetic polymers, vast polymers were used to modify DNA materials for bone regeneration, such as alginate, chitosan, proteins (eg. fibrin, silk, and collagen), glycosaminoglycans, polylactides (PLA), polyglycolides (PGA), co-polymers PLGA, polycaprolactone (PCL), and polyethylene-glycol (PEG).– When these complex materials were used in cells or organs, cellular uptake via endocytosis is the first challenge, since the efficiency and process of cellular uptake depend on the cell types and the physicochemical properties of the complex materials, such as the surfaces of cell and materials, and the shape and size of materials., The mechanisms of endocytosis are diverse, including both caveolae and clathrin dependent, micropinocytosis, and independent mechanisms. For DNA nanomaterials without any modification, when they are internalized by cells, the first existing form within cells is early endocytic vesicles, which can be rapidly acidified and thereby form late endosomes, and then DNA nanomaterials will be degraded by lysosomes (Fig. 2). Those nano-viral vectors mentioned above have some excellent properties, such as being non-immunogenic, high cellular uptake, outstanding endosomal escape, and rapid gene release.– However, these studies mainly focused on the gene delivery and release, the investigations of the biological application in bone regeneration were limited in cytology experiments and small animal experiments, primarily the pre-clinical trials. The gene release processes of some delivery systems were even unclearly conducted and demonstrated. More importantly, the underlying mechanisms and the biosafety of these DNA materials combined with other scaffolds in bone regeneration remain poorly understood, and the effects on bone tissue regeneration of these nanomaterial complexes should be elucidated in further investigations.

Neural tissue engineering

27Neural tissue is considered as the vital system for all lives. For human being, neurodegenerative disorders and damages to neural tissue can result in severe and permanent disabilities,, bringing heavy burdens for individuals, families, and socity. Owing to the lack of regeneration ability and complicated connections between different physiology systems, it is a great challenge to recuperate injured neural system, and make it work normally.,– Therefore, neural tissue engineering has emerged as a potential remedy with great capacity in repairing and regenerating nerve tissue injuries. In recent decades, biocompatible materials have been largely employed to achieve the regeneration and functional recover of injured neural tissue. Some successfully synthesized nanomaterials can provide mechanical support for neurite growing and inhibit the formation of scar tissue, affect biological cues to steer the growth of axons, promote regeneration, and incite the integration with the resident healthy tissue., Currently, the natural (e.g., collagen, gelatin, hyaluronic acid, and alginate) and synthetic nanomaterials (e.g., PLA, PGA, PLGA, and PEG) are considered as neural scaffolds for their biocompatible and biodegradable properties.– Those nanomaterials could also combine with some specific DNA materials to obtain other positive effects for gene delivery or cell activation in neural tissue regeneration (Fig. 1a, f).,–

28The applications of gene therapy with DNA materials in neural tissue regeneration are also significant, and the pDNA is the most common material used.,, Feng et al. reported an injectable two-stage gene delivery system, which consisted of a nanofibrous micro cell carrier and a self-assembled nano-sized polymer, and found that the combination of the two-stage pDNA delivery system could promote intervertebral disc (IVD) regeneration and suppress the fibrosis (Fig. 1f). In this study, the pDNA was loaded with orphan nuclear receptor 4A1 (NR4A1). The NR4A1 was demonstrated as a safe and efficient gene agent with pleiotropic regulatory function to restrain pathogenic fibrosis, which was associated with vascular homeostasis,, inflammatory responses,, and metabolism of lipid and glucose.– Taniguchi et al. reported a synthetic DNA-binding inhibitor with the ability of targeting vital cell differentiation controlling genes, and demonstrated that the DNA-binding inhibitor could target the SOX2 gene. The downregulation of SOX2 gene could trigger pluripotent stem cells differentiate into the mesoderm, which could form the notochords to wrap neural tubes. Wang et al. developed a DNA aptamer, named yly12, which could strongly target neurites. The aptamer yly12 could bind neural cell adhesion molecule L1 (L1CAM), which was expressed in normal neural tissue as surface antigen. Therefore, the aptamer yly12 could be used as a potential molecular probe to investigate the development of nervous system and the diagnosis of neurological diseases. Shea et al. used the poly(lactide-co-glycolide) (PLG) delivery DNA complexes to achieve gene delivery. In this study, the neurons and accessory cells were co-cultured together to measure the outgrowth progress of neurites when the PLG-DNA substrates were applied. Shea et al. found that surface immobilization of PLG-DNA substrates, which were modified with pDNA as the gene carrier and deliver systems, could promote the transgene expression and the regeneration of complicated neural system. In other studies, some nanoparticles (e.g., magnetic nanoparticles (MNPs), magnetic core-shell nanoparticles (MCNPs), and gold nanoparticles (AuNPs)) loading pDNA or RNA (e.g., short interfering RNA (siRNA)) were used to deliver genetic materials into neural stem cells (NSCs) and guide cell differentiation.– Till now, although the above-mentioned work has presented numerous nanomaterials modified with different DNA materials, their applications in neural tissue engineering are still greatly limited, becasue the work is at the initial stage and the results are prelimilary. The mechanisms of different DNA-based and DNA-modified nanomaterials studied in neural tissue regeneration remains unclear. However, these studies intiated the step by providing the design principles for DNA-based and DNA-modified nanomaterials that were used in in vitro and in vivo nerve regeneration.

29Recently, TDNs were reported as promising DNA nanomaterials for neural tissue regeneration (Fig. 1f).,, In these studies, it was demonstrated that NSCs treated with TDNs could exhibit enhanced cell proliferation, migration, and neuronal differentiation., In the in vivo experiment, a concomitant approach of NSCs and TDNs was applied in the animal model of spine cord injury (SCI). The study found that the TDNs possessed the capacity to increase the cell survival of the transplanted NSCs, and the concomitant approach of NSCs and TDNs could improve the recovery of motor function and the neural tissue regeneration in the injured site of spine cord. These results provided an interesting treatment strategy for neural tissue regeneration. Furthermore, Lin et al. also reported potential neuroprotective effects of TDNs on the cell models of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD).,, Although these results were prelimilary, they might provide a promising synergistic agent for treating nerve damage and degenerative diseases. For futher studies, we would believe that TDNs and other DNA nanomaterials might be used to deliver some functional drugs and DNA/RNA sequences to the neural tissue for disease therapy.

Skeletal and cardiac muscle engineering

30The obligations of skeletal and cardiac muscle are to support the body movements and blood circulation, where the chemical energy of nutrients are turned into kinetic and heat energy. Although the skeletal and cardiac muscle are both differentiated from the mesoderm, physiology and morphology properties of them are dissimilar. Lack of regeneration ability, the adult mammalian cardiac muscle could not self-renew when some injuries happen, such as heart attack.– In contrast, skeletal muscle tissue can naturally repair minor injuries by self-regenerating, thanks to the property instigated by the activation of residual stem cells named satellite cells.– However, severe damage and some myopathies can result in irreversible loss of muscle and functional disorder.,, Current therapies of broken skeletal muscle and some myopathies include injection of in vitro cultivated muscle cells and autologous skeletal muscle transplantation, but with many limitations in clinical applications of treating patients.,– In some previous studies, it was reported that some biomaterials could stimulate skeletal muscle regeneration via supplying chemical and physical cues to muscle cells, which could mimic the natural cascade of muscle tissue regeneration.,,, The possibility of skeletal muscle regeneration is of great promise in curing the movement disability of bones and muscles, and novel medicines/biomaterials with some positive effects on cardiac muscle, such as protective effects from drug toxicity and hypoxia injury, are also of great significance in treating heart diseases.

31In recent studies, DNA-based nanomaterials were used for regenerating skeletal muscle and exerting protective effects from hypoxia injury of cardiac muscle, respectively., Wang et al. creatively developed a fancy near-infrared light-activated DNA agonist (NIR-DA) nanodevice (Fig. 1c). The NIR-DA system could deliver the cell signaling by nongenetic manipulation, and change the tissue phenotype of deep sites by activating the receptor tyrosine kinase (RTK), which enables the control of cell polarization, cytoskeletal remodeling, and directional migration. The study demonstrated that NIR-DA system could be employed in vivo to regulate RTK signaling, cell migration, and myogenesis of skeletal muscle satellite cells. Therefore, the NIR-DA system was regarded as a promising regeneration medicine for skeletal muscle injury.

32Blumenfeld et al. reported a new-style covalent attachment of genomic DNA to iron-oxide nanoparticles. These magnetic nanoparticle complexes could capture some chemotherapy agents from human serum, including cisplatin, epirubicin, and doxorubicin (DOX). It was found that the DNA-coated nanoparticle complexes could protect cultured cardiac myoblasts from the lethal levels of chemotherapy agents, which could be developed as substrates for medicine capturing. Zhang et al. found the cardio-protection effects from myocardial ischemia-reperfusion injury (MIRI) by taking the advantage of the anti-inflammatory and antioxidative potential of TDNs (Fig. 1e), which could suppress the expression of reactive oxygen species (ROS) and then weaken the oxidative damage and apoptosis of cardiomyocytes. These studies offered some new ideas of using DNA-modified nanomaterials for treating cardiovascular and cerebrovascular diseases., Although the applications of DNA-based nanomaterials are few in this aspect, an innovative research design idea was provided by these studies for the skeletal and cardiac muscle engineering.

Skin tissue engineering

33Skin, the biggest organ covering the entire body, consists of the epidermis and the dermis, with a complex blood supply and nerve innervation., For the resident stem cells in skin, the functions include hair regeneration, epidermal homeostasis, barrier resistance, and wound repair., Therefore, the health of skin organ is a significant element for human.– The injuries of skin commonly happen with causes including burn, surgical operation, traumatism, chronic skin disease (e.g., parapsoriasis guttata and vitiligo), aging, systemic diseases (e.g., chronic kidney disease (CKD), hypertension, diabetes, and rheumatologic or inflammatory disease), infection (bacterial or fungal) and dermatitis.– Nowadays, promoting the wound healing in skin is hot in clinical research, which can be affected by the interaction of several cells, growth factors, and cytokines.– Some biomaterials have the abilities of the biomedical functions and tissue regeneration engineering, including implantable devices and some drug and gene delivery.– Furthermore, some biomaterials were combined with DNA nanomaterials to overcome some shortcomings and enhance positive effects of these materials in biological application., DNA biomaterials applied for skin regeneration have also been widely studied in different skin diseases (Fig. 1b).,–

34For the therapy of full-thickness burn wounds, Gao et al. used the pDNA encoded VEGF-165/N,N,N-trimethyl chitosan chloride (TMC) complexes to load a bilayer porous collagen-chitosan/silicone membrane dermal equivalents (BDEs). The cells treated with TMC/pDNA-VEGF complexes could highly express VEGF gene and quickly promote wound healing. For diabetic chronic wounds, Lou et al. put the gene of pDNA-VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent (BDE), and the DNA complexes showed the effective transfection abilities to promote the expression of VEGF gene, which could then promote the angiogenesis and change the immunomodulation. This study showed that the gene-activated bilayer dermal equivalents (Ga-BDEs) possessed the versatile potentials for accelerating wound healing of diabetic chronic wounds. Furthermore, Li et al. used hydrogel embedded with resveratrol (Res) and pDNA-VEGF (Gel-Res/pDNA-VEGF) to promote the healing of splinted excisional burn wounds. The Gel-Res/pDNA-VEGF was proved to possess the abilities to enhance the formation of microvascular and suppress the inflammation response. Additionally, the pDNA of basic fibroblast growth factor (bFGF; pDNA-bFGF) was also widely studied.,,– Li et al. applied nanofibers (poly(l-lactic acid)/polyhedral oligomeric silsesquioxane (PLLA/POSS)) to load pDNA-bFGF and pDNA of angiopoietin (pDNA-ANG). The PLLA/POSS/pANG/pbFGF (Fab) composite nanofibers presented the capacities to promote revascularization of the deep skin defect healing. As reported, the electrospun core-sheath fibers loaded with pDNA-bFGF could promote skin regeneration in diabetic rats. Furthermore, dual delivery systems of the pDNA-VEGF, pDNA-bFGF, or pDNA-ANG were applied to promote regeneration of different skin defects.–

35Fan et al. reported that TDNs (sizes ≤ 75 nm) could effectively penetrate the skin of mice and human, and reach dermis layer, which could load and deliver DOX to subcutaneous tumor site. This study inspired that TDNs could deliver other drugs to treat more subcutaneous tumors. Zhu et al. demonstrated that TDNs could promote fibroblast (HSF cell line) and keratinocyte (HaCaT cell line) growth and migrating. In addition, TDNs could promote the secretion of VEGF and bFGF and enhance the wound healing. Therefore, TDNs might be an novel DNA materials with the potential in skin tissue regeneration and drug delivery for subcutaneous tumors.

Other tissue engineering

36Beyond above-mentioned tissue engineering applications, the DNA materials also have been used in vascular tissue and ocular tissue.,– Angiogenesis is important for other tissue regeneration, such as bone, muscle, and neural tissue. Abundant blood supply can enhance the nutrition supply for different tissue regeneration. For angiogenesis, materials loading pDNA or DNA aptamer are widely studied. Mao et al. used N,N,N-trimethyl chitosan chloride (TMC) that was modified with pDNA-VEGF to promote VEGF gene expression and thereby effectively enhance the angiogenesis. The increased angiogenesis could also be promoted by some scaffolds containing both pDNA-VEGF and pDNA-FGF2., Son et al. developed aptamer-conjugated hydroxyapatite (Apt-HA) to promote angiogenesis and bone regeneration. In recent years, TDNs were employed to promote angiogenesis in vitro and the model of the jaw bisphosphonate-related osteonecrosis.– Although the DNA-based complexes applied for angiogenesis are in their early stages, DNA-based materials might be developed as regeneration medicine to promote angiogenesis in different tissues.

37As for the research on ocular tissue, the number of studies keeps increasing in recent years, indicating growing interests and great potential of applications for ocular tissue regeneration and ophthalmic drug delivery (Fig. 1d). Heremann et al. combined DNA and nanoparticles as DNA-based complexes to treat eye infections, which was the first report describing the usage of DNA-based carrier systems in ophthalmic drug delivery. Then, PEI-DNA nanoparticles were employed to deliver corneal gene, with great efficiency in gene delivery for the corneal gene therapy. AuNPs-encoding pDNA were used to transfect human retinal pigment epithelium cells. Furthermore, TDNs were used to facilitate the corneal wound healing, promote the re-epithelialization of wounds, and improve the corneal transparency. Cai et al. reported that TDNs could prevent retina ischemia-reperfusion injury from the oxidative by reducing the ROS. Moreover, Gao et al. proven that TDNs could induce the immine tolerance and prevent the onset of Type 1 diabetes (T1D). For T1D occurring with T cell-mediated autommune, inhibition of autoreactive T cell and inducing regulatory Tregs to rebuild the immune tolerance are the two promising strategies. In this study, the researchers reported that the TDNs could control the level of glycemis, protect β-cell, and prevent the onsed of T1D by regulating the immunity. Therefore, some DNA nanomaterials might possess the abilities of immunomodulation for some immune diseases. The regeneration and protection of the ocular tissue are vital for human healthcare, and DNA-based nanomaterials will maintain attractive in this field in the following years.

Drug delivery and tumor therapy

38In recent decades, DNA nanotechnology has also made amazing progress in biomedical applications in drug delivery and tumor therapy. In this part of the review, the development trajectories and latest advances of pristine DNA-based nanostructures will be highlighted.

39Compared with conventional nanoscale drug carriers, such as gold nanoparticles and liposomes, DNA-based nanostructures are more suitable candidates characterized by high biocompatibility, structural diversity, low cytotoxicity, high accessibility, and capability of penetrating cell membranes without transfection.– Owing to their nucleotide-composed backbones and flexible joints, DNA-based nanostructures possess high editability and modifiability. They can be built into arbitrary constructions like stacking building blocks., According to their intrinsic natures, multifunctional ligands can be integrated into frameworks through different ways, including conjugation, intercalation, encapsulation and loading., Thus, numerous assemblies of DNA nanoparticles were developed and further applied to multiple biomedical fields, especially in drug delivery (Fig. 3)., In the following, diverse DNA nanoparticles applied in biomedicine are listed and illuminated (Table 2).

DNA polyhedron and origami

40Since the first closed DNA polyhedron (poly-DNA) developed by Seeman et al., multifarious DNA-based predetermined motifs (tubes, buckyballs and prisms) were created.– By means of DNA origami technique, the long scaffold ssDNA coupled with short and flexible staples provide more conceivements for different DNA motifs. For further developments and applications, poly-DNA was served as a nanocage to accommodate pharmaceutical molecules owing to its inherent spatiality.– Extended sticky ends can also be designed for the attachment of additional aptamers, biotins or valuable peptides thanks to their modifiable external surface. With the modification of available ligands, it holds great promise in tumor targeted therapy.

41It is common to utilize DOX to form a drug-DNA nanocomplex. For instance, Hogberg et al. employed two types of DNA tubes (straight and twisted with different numbers) for carrying DOX and compared their carrying performance. Triangular DNA and tubular DNA of different forms were constructed as a vehicle to deliver DOX into cancer cells for effective cancer therapy. Folic acid (FA) coupled with DOX were also linked to TDNs, which indicating the excellent delivery abilities of TDNs.

42A DNA rectangle bent into a hollow DNA tube, and the butt seam of which was fastened with AS1411 (a DNA aptamer). Its open state depended on the affinity of aptamer with the nucleolin targeting. With the structural separation, inner thrombin was exposed selectively to induce blood coagulation and cause cell death by vascular occlusion. Biocca et al. reported that truncated DNA octahedron (octa-DNA) could be recognized by low-density lipoprotein receptor-1 (LOX-1) because of its similar property with oxidized low-density lipoprotein (ox-LDL). It could thereby invade into LOX-1 related cells via substrate-receptor mechanism, which indicated the inherent targeting property of octa-DNA. Huang et al. proposed a unique DNA icosahedron (icosa-DNA) that was composed of six-pointed star skeleton. MUC1 aptamer was appended to its primary synthetic unit, and DOX was simultaneously embedded into double-stranded docking sites. This MUC1-DOX modified icosa-DNA could distinguish the MUC1-positive cells and achieve controllable release of DOX intracellularly.

43As the non-stop development, multiple-bundle DNA-based nanostructures for different purposes appeared. An aptamer-Epirubicin (EPI) DNA dendrimer was designed by Khalil et al. Distinctively, more than two aptamers (AS1411, MUC1 and ATP aptamers) coupled with Epi were embraced in this bracket, equipping it with multitargetness and potent cytotoxicity.

Applications of TDNs in drug delivery

44Among multitude architectures, TDNs is of the greatest interest.,,– Owing to its tripod-shaped framework, excellent structural stability was conferred so that it could resist deformation under enzymatic digestion. As for the synthesis of TDNs, several synthetic schemes were put forward, and TDNs of different sizes were successfully produced.,, These products were examined with potential to remedy many disorders. In previous studies, aptamers (such as AS1411, anti-HER2 aptamer (HApt), and SL2B), antibodies and proteins (affibody, FA) were conjugated with TDNs for cancer cell recognition and inhibition.– Coupled with the loading of therapeutical agents like 5-fluoroutacil (5-FU), DOX, paclitaxel (PTX), the products were supposed to selectively enter cancer cells and exert potent antitumor effects.,,

45As a proof of concept, HApt was linked with TDNs to anchor HER2-overexpressed cancer cells. HER2 is a member of transmembrane proteins, and a hub for signal transduction pathways among cancer cells. Its overexpression is associated with malignancy and the poor prognosis of breast cancer. According to previous work, HApt could be specifically chosen to bond with HER2 and supress its expression., With this in mind, HApt-TDNs was prepared to specifically combine with HER2 and then transfer it into lysosome for the following degradation. This behavior consequently contributed to cell apoptosis and inhibit tumorigenic growth. Compared to simple HApt, the stability of this nanocomplex was considerably improved and response time was prolonged. It might stand for a new perspective in breast cancer therapy. In addition, a tailored affibody molecule was built to mimic the structure of monoclonal antibody, which was confirmed with specificity to target HER2. With the additional intercalation of DOX, this DNA-affibody-drug chimera showed excellent specificity and inhibition to HER2-overexpressed cancer cells.

46With regards to aptamers, G-quadruplex aptamer (AS1411) was the representative one that was systermatically investigated. It was equipped with both targetness and pleiotropic antiproliferation through its combination with targeting receptor-nucleolin (NCL)., It could be directly attached to the vertice of poly-DNA or linked with the ssDNA to form an overhang at the edge of 3D structure. These AS1411-modified poly-DNA could act as an effective drug carrier or a nanomedicine with targeting ability for therapy. Studies have also been concentrating on the structural upgrading of TDNs.– AS1411 and 5-FU were simultaneously conjugated to TDNs to establish a splendid nanomedicine that specifically inhibit the cell viability of NCL-overexpressed cancers.

47SL28 is a VEGF-165-related DNA aptamer. Its dimerization with VEGF-165 plays an important role in angiogenesis in vivo. Zhao et al. presented a dual-targeting nanosystem for SL28 and FA, the cooperation of which could obviously improve targeting ability of nanosystem towards colon cancer cells. With a follow-up loading of DOX, the synergic antitumor effect was obtained. Liu et al. united MUC1-probe and AS1411 with TDNs, as well as the payload of DOX. The selective MUC1 aptamer-protein binding induced an unwinding of quenched sequence and fluorescence recovery to differentiate MUC1-positive cancer cells. The follow-up AS1411-nucleolin bound caused its translocation into nucleus and DOX release intranuclearly. This superior combination carved a path to cancer theranostics. Furthermore, temozolomide (TMZ) loaded TDNs along with two DNA aptamers (AS1411 and GS24) for glioblastoma treatment was reported. GS24 was reported to be a transferrin (TRF) aptamer of 64 nt in length. Owing to its unique spatial structure, TRF on cerebrovascular endothelial cells of BALB/c nude mice can seize and combine with GS24, and thereby pass through cerebrovascular barrier. Specifically, after injection with this nanointegrate, the function route was as follows: firstly, it moved across the blood-brain barrier (BBB) of mouse and permeated into brain parenchyma via receptor-mediated transcytosis; secondly, the assistance of AS1411 enabled it to enter the cell nucleus, and then offloaded TMZ for its lethality towards tumor cells, which could alleviate the resistance and myelosuppression of TMZ at the same time.

48Other elements including metal complex and photosensitizer were also added as adjuvants to substantially enhance the medical effects of TDNs. Tian et al. employed a dual aptamer-tethered TDNs for carrying metal compounds. A representative platinum agent-[Ir(ppy)2phen]+PF6 (Ir) was loaded onto MUC1- and AS1411-modified TDNs. It anchored glioma cells to destroy their vascular mimicry processes and cause cell death through mitochondrial and ROS pathways, which contributes significantly to glioma therapy.

49In addition to routine drug treatment, photodynamic therapy (PDT) is a minimally invasive means, which is frequently used in tumor therapy. Photosensitizers including porphyrinoid and cyanines can be activated under irradiation, thereby produced excess ROS and ultimately drove cancer cells to necrose. When they are attached to or loaded on TDNs, their disadvantages such as low stability, poor solubility and tissue penetration were greatly minimized. Methylene blue (MB) and BMEPC, which are commonly used as imagine probes and methemoglobinemia agents, can also interact with TDNs and DNA origami. Subsequently, when the preprocessed tumor tissues were exposed to light, a satisfying cytotoxicity against tumor cells would be observed.

50Other than chemical agents, the delivery of antisense oligonucleotides (ASOs), proteins and RNA are also spotlighted. Dual-bundle TDNs with targeting peptides and ASOs were reported to effectively deliver ASOs into nucleus of tumor cells. The increased release of ASOs could lead to an enhanced cytotoxicity and the knockdown of proto-oncogene c-raf. Studies regarding small interfering RNA (siRNA) were also reported.,, Similar DNA nanoparticles with cancer-targeting peptides were utilized to accurately transport siRNA into tumor cells and trigger related genes silencing. The low expression of particular genes is the main inducement of cell inhibition.

51In addition to the above-mentioned, TDNs were also proved to affect various pathological courses. Lin et al. reported that TDNs could modulate the M1 polarization of macrophages into an appropriate level, avoiding an exaggerated inflammatory response. It also exhibited antioxidative and anti-inflammatory potentials through suppressing mitogen-activated protein kinases (MAPK, including JNK1/2/3, ERK1/2, and p38 family) and upregulating the expression level of HO-1, which is associated with anti-inflammation, anti-apoptosis and antioxidation.

52In the microbiological researches, TDNs have sparkled as a component of innovative antimicrobial agents. With the advent of superbugs, bacterial resistance caused by antibiotics abuse has become so acute that effective measures should be immediately taken to prevent the deterioration of this condition. An antisense peptide nucleotide (asPNA) with high stability and affinity was proposed to inhibit the transcription of an intended bacterial gene (ftsZ). Its encoded protein (FtsZ) was confirmed to be involved in bacterial cell division and has been used as a validated target in bacterial prevention. Lin et al. incorporated asPNA with TDNs to deliver it into methicillin-resistant Staphylococcus aureus (MRSA), interfere the expression of ftsZ, and subsequently result in bacterial growth inhibition. Although humans are collective organisms with microbes, the colonization of bacterial biofilm is a decisive factor of chronic inflammation, which is the main culprit of critical illnesses in essential organs. Microbial communities form compact biofilms, along with exopolysaccharides (EPS) and other extracellular matrix, to protect themselves from antibiotics. Therefore, the most fundamental method to diminish the vitality of bacteria is to prevent the initial formation of bacterial biofilms. The same study group designed an ASOs on the basis of VicK protein binding domains to regulate the secretion of EPS for early prevention against biofilm formation. It could specifically target gtfBCD (from glucosyltransferase gene family), gbpB, and ftf genes, which encoded a series of Streptococcus mutans biofilm formation proteins, a glucan-binding and an adhesion-associated protein, respectively. Similarly, ASOs were carried by TDNs to degrade the expression of targeted genes and availably block EPS production, which were both prerequisites for initial stage of biofilm.

DNA intelligence nanodevice

53Along with the progress in DNA nanotechnology, deoxynucleotides were concatenated, folded, and assembled into a more intricate, multifunctional and intelligent nanodevice. Primitively, Tan et al. created X-Y-shaped DNA nano-assembly and aptamer modified DNA nano-train. For the former, three branches of Y-shaped DNA units were developed to link or intercalate with aptamers, drugs or oligonucleotides, and the chimera then jointed in the X-shaped central bonder through predesigned supplementary arms. After compact crosslinking of these X-Y-shaped building blocks, a simple nano-assembly with targeting and multiple drug resistance (MDR) reversion ability could be obtained. The latter one was composed of two hairpin-patterned DNA sequences (M1, M2) and an aptamer trigger. The hybridization of M1 and M2 was initiated by the mixture of chimeric trigger, resulting in a nano-train with a chimeric aptamer locomotive and many chambers for drug loading. The same group intensively studied a noncanonical DNA nanoflower (NFs) without following Watson–Crick. It was self-assembled from DNA concatemers generated by rolling circle replication and the building template could be tailored with the attachment of functional moieties for biotherapy and bioimaging, etc. DOX and aptamer sgc8c were embedded and incorporated into NFs to recognize PTK-overexpressed cells and exert therapeutic effects. The optical labels could be similarly applied for fluorescent imaging. Moreover, several novel DNA nanocircuits were also established. The trigger sequence linked with the aptamer could precisely activate a series of related cascade reactions in target cells to eventually produce therapeutic effects.

54Xu et al. fabricated a DNA nanocomplex with a trunk and several legs, resembling a centipede. Two hairpin sequences constituted a DNA scaffold through hybridization chain reaction (HCR) to form a long DNA trunk, providing abundant docking sites for pharmaceutical molecules. Aptamers such as Zy1 were combined with the trunk-like couples of legs via streptavidin-biotin affinity. It could grasp hepatoma cells SMC-7721 and release the payload to influence the cell activity. Theoretically, this nanocentipede could be further used in multivalent drug delivery.

55Moreover, smarter 3D architectonics designed for drug containers like DNA boxes were set up with movable switches. Their hollow constructions provide sufficient spaces for functional cargoes. Contents could be reversibly exposed or manageably released under genetic, optical or many other biochemical triggers. Additionally, more sophisticated lock-and-key systems were fabricated to control the accessibility of cargoes or for controlled reaction rate as required. Their structures were also refined to the greatest extent so that they could readily pass through the biological barriers in vivo.

56For DNA nanodevices illustrated above, the appended molecules were mostly replaceable, revealing that they were superior to drug carriers with broad feasibility. However, the microstructures of the combination between DNA nanomaterials and different drugs cannot the clear observed.

DNA nanohydrogels

57As for particle size, apart from individual nanoscale structures, micron-sized DNA polymers were constructed via liquid phase crystallization and dense packing of dsDNAs instead of Watson–Crick base-pairing., Thus, they exhibit excellent monodispersity and biocompatibility. Tan et al. proposed a multi-module DNA nanohydrogel with one linker and two functional monomers. The size could be adjusted by controlling the ratio of building units. Elements including aptamers and genes could be incorporated to build an efficient nanomedicine. Hitherto, not just linear as nanowires, other devisable and rigorous nanostructures have been obtained. They were applied extensively in both biosensing and biomedicine, and would be further utilized in biological nanotechnology.

Switchable DNA nanomachine

58In order to meet the growing demands, mechanically controlled DNA nanomachines with operational strands that could be switched on and off by active domains emerged.– For instance, complementary fuel strands were designed to initiate DNA tweezers. Their hybridization and removal enable these tweezer-like machines to open and close reversibly. In addition, the structural transformation could be triggered by following fuses: changes of pH, light excitation, binding with specific sequences or incorporating with proteins, aptamers or other functional ligands. A pH-dependent DNA origami plier with two levers connected at a fulcrum was observed to transform according to pH value. Its X-shaped open state could turn into parallel or antiparallel closed form in response to acidic conditions.

59At present, a new concept-DNA nanorobot is emerging. It refers to an array of highly intellectual nanodevices. They could be equipped with multiple functions through precision assembly. The mode of action was controlled by organized switching system, which includes but was not limited to simple on-off setting, and the logic gates (AND, NOT, OR, etc.) could also be set up., Thubagere et al. devised an autonomous DNA robot for cargo sorting. Unlike previous ones that walked following a prescribed route, it could walk towards different directions randomly without energy supply for automatic cargo detection and classification. Three building blocks were designedly composable to select various cargoes at uncertain locations and classify them into two groups. This sorting task could be carried out on the surface of a 2D DNA origami sheet. In more sophisticated scenarios, several robots could be assigned to work cooperatively. When it comes to other molecules, such as antibodies, proteins or nanoparticles, promising applications including molecular computation and biomedical diagnosis can be explored.

Multi-drug resistance (MDR) reversion

60DNA-based nanostructures can not only achieve effective delivery of chemical agents to tumor sites, but also reverse multi-drug resistance (MDR) in cancer cells. MDR, either inherent or acquired, has always been a tough challenge in drug development and utilization. To overcome it, multifarious drug combination strategies are proposed and different drugs are formulated, but their effects are not that satisfactory. The causes of MDR are extremely complex, including DNA repair, decreased drug flow and detoxification. According to previous studies, the most common reason for this is the excessive efflux pumps, which can eject drug and result in ineffective., Taken together, the fundamental way to bypass this efflux-pump mediated MDR is to improve drug concentration in the pathological areas.

61DNA-based targeted drug delivery system has become a focus worldwide because of its ability to increase drug accumulation specifically in cancer cells via enhanced permeability and retention effects (EPR). It proved that DNA nano-systems could enter cells through caveolin- and clathrin-mediated endocytosis, independent of efflux pump pathway. Therefore, their high delivery efficiency can be expected to reverse obstinate MDR observed in most drug tests.

62Conventional agents such as DOX, PTX, 5-FU have been confirmed to elicit MDR in tumor cells during their long-term use. Investigators have been striving for a more optimized program-various types of DNA nanoparticles that were applied for DOX resistance.– As a consequence, DNA origami was reported to show better performance in delivering effective levels of DOX than poly-DNA owing to its higher density of DOX in more abundant docking sites. DOX loaded rod-like, X-Y-shaped DNA origami and an apt-NFs nano-assembly were fabricated for human leukemia/MDR cells, respectively. A DOX loaded TDNs was found to inhibit MCF-7/MDR cells activities. MDR reversion in these cases were achieved through efflux evasion, which directly enhanced local drug concentration, and thus, extended effective action time and reduced the general toxic effects. Additionally, Ding et al. constructed 2D (DNA triangle) and 3D (DNA tube) nanostructures to carry DOX. Both of them could improve drug sensitivity of DOX/MDR human breast cancer cells through efflux pathway. They were verified to be able to prompt drug molecules to disperse into active sites through elevating lysosomal pH.

63PTX loaded TDNs (PTX-TDNs) presented by Lin’s group was surprisingly valuable for treatment of PTX/MDR non-small cell lung cancer. It exerted cytotoxicity towards PTX/MDR cancer cells through downregulating the expression of P-glycoprotein (P-gp), a membranal transporter associated with drug efflux. In other words, PTX-TDNs could increase intracellular excretion of drugs in MDR cells, resulting in potent microtubule polymerization and cell apoptosis.

Immunostimulatory effect

64Similar to aptamers and drugs, ligands with immunostimulatory (e.g., CpG), or catalytic activities (e.g., enzyme) can be appended to DNA frameworks. Since the basic component of DNA nanoparticles is deoxyribonucleic acid, they exhibit low immunogenicity and their internalization would not intensify immunoreaction. Unmethylated CpG oligodeoxynucleotides can be recognized by mammalian immune system because of its existence in bacterial or viral genome., It can specifically combine with Toll-like receptor 9 (TLR9), and activate it allosterically, which subsequently induce cascade reactions and promote the secretion of remarkable cytokines and chemokines, including interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α)., Thereout, DNA-CpG nanosubstance was conceived an immunomodulating nanomaterial (Fig. 4).

65DNA nanotubes, of different dimensions and DNA dendrimers, with CpG were reported in previous studies. Fan’s team attached CpG to four ssDNA building units and prepared a CpG-bearing TDNs. Variform DNA nanoribbons based on rolling circle amplification (RCA) technique were proposed by the same group as well.

66In general, macrophages along with dendritic, monocytes and mast cells are of great significance in maintaining immune homeostasis and play an important role not only in autoimmunity, but also in inflammatory diseases, metabolic disorders, neoplasia, anaphylaxis and wound healing. CpG-modified DNA-based nanostructures could enter immune cells, including macrophage RAW264.7 cells noninvasively and efficiently, and keep intact in their endosomes, whereupon trigger enhanced immune responses. Through this activation process, they were expected an alternative to surmount tumor-associated immunodepression and regulate essential pathological reactions. Afterwards, CpG was respectively linked to ssDNA, dsDNA, Y-shaped DNA (Y-DNA), and three types of dendritic DNA (DD-DNA)., In the literature, Y-DNA with three dendritic branches served as a single element in DD-DNA’s building-up process. One Y-DNA was ligated to three other duplicates to obtain a primary DD-DNA (D1). One D1 was thereby ligated to another six Y-DNA to form a secondary DD-DNA (D2). By that analogy, tertiary DD-DNA (D3) was synthesized. It was noteworthy that individual Y-DNA, D1, D2 and D3 without CpG were substantiated to have intrinsic immune activation properties, and there was an increase with the growth of branch number, maybe partially due to their increased uptake by macrophages. Then, CpG were positioned on the outermost layer of each structures. In other words, D1 (CpG), D2 (CpG) and D3 (CpG) were decorated with 6, 12 and 24 CpG sequences, respectively. Detailed experiments revealed that the secretion levels of TNF-α and IL-6 were strikingly increased in DD-DNA (CpG) and Y-DNA (CpG), compared to ssDNA (CpG), dsDNA (CpG) and simple mixture of several CpG sequences. However, the increasing trends were not proportional but much higher than the enhanced immunoreaction triggered by non-CpG structures. It was indicated that the immunostimulation of CpG motifs could be greatly amplified by the structural characteristics of Y-shaped DNA dendrimer. A similar profile was detected in the comparison of Y-DNA modified with 1 and 3 CpG motifs. Thus, more CpG motifs on one architecture might stimulate stronger immune response. This finding was then extensively applied to inhibit the growth of tumor cells. After adding Y-DNA (CpG)-treated RAW264.7 cells, a significant decrease was observed on the number of murine melanoma cells. To clarify the relationship between structural features and biological properties, the same team established some other polypod DNA (p-DNA). They used 3 to 12 oligodeoxynucleotides of different lengths to generate tri-, tetra- to dodecapods DNA of different sizes, and CpG was attached in a similar way. Through rigorous examinations, it was discovered that p-DNA with more pods entered RAW264.7 cells more easily. The release levels of TNF-α and IL-6 showed the same trend, and an increasing order was found in tri-, tetra-, penta-, hexa- and octapods DNA, which symbolized a stronger activation of immune response. These results provided definite evidence that the growing number of pods had an impact on activating the level of immunostimulation.

67To the best of our knowledge, the invasion of foreign substances would cause varying degree of host immune defense. In general, it manifests as an excess secretion and accumulation of inflammatory cytokines, which is the origin of systemic complications. To explore the immunological role of TDNs, previous studies established lipopolysaccharides (LPS)-induced inflammatory cell model to act RAW264.7 cell line. After retreatment with TDNs, the production and the expression of nitric oxide (NO) and inducible NO synthase (iNOS, closely related to NO production) were decreased and downregulated to regulate NO within a normal concentration. Herein, it could be inferred that TDNs is an outstanding biomaterial without immune rejection. Based on this, Chang et al. utilized TDNs as an antigen platform for vaccine. As CpG conventionally serves as an adjuvant in vaccine for immunotherapy, Chang et al. assembled an antigen-streptavidin (STV), CpG and TDNs into a vaccine complex (SCT). Both in vitro and in vivo studies showed that STV and CpG could be more easily internalized by antigen-presenting cells due to the application of TDNs delivery system. Then, more T cells were activated, facilitating the differentiation of STV-related B cells and the production of relevant antibodies. Importantly, the 3D architecture of SCT could render a close proximity of adjuvant and antigen, which highly augmented immunogenicity of the vaccine. Given results above, DNA-based nanosystems maintained an impressive immunostimulation potential that might be further utilitized in immunotherapy and vaccine development.

Biosensing, biodetection, and diagnosis

68Early diagnosis of diseases is of great importance in developing timely and effective treatment stragety to prevent deterioration and cure illness., The traces of intracellular molecules, proteins or nucleic acids have great benefits in disease prevention, diagnosis and therapy. Conventionally, experimental approaches such as western blotting to assay their expressions are time-consuming and laborious. Micromolecular probes that can achieve real-time detection and dynamic imaging are preferable. A robust probe delivery vehicle is on demand to conquer the instability of simple probes. More recently, DNA-based nanostructures show extraordinary promise in molecule detection and biomedical imaging (Fig. 5).

69Generally, aptamer-based DNA diagnostic nanodevices were widely explored. TDNs, square, pentagon-based pyramids and prisms were incorporated with Plasmodium falciparum lactate dehydrogenase (PfLDH) aptamer and fluorescent labels to distinguish malaria biomarker- PfLDH from human lactate dehydrogenase. Recent progress has been made that angiopep-2 (ANG) linked TDNs (ANG-TDNs) was a potential imaging medium for brain tumors. Owing to the high affinity of ANG with low-density lipoprotein receptor protein-1 (LPR-1) on brain endothelial and glioma cells, ANG-TDNs was able to cross BBB and recognize cancer cells, and combined ues of luminescent dyes could specifically label brain tumor regions.

70In Argonaute2 (Ago2) detection, Zhang et al. designed a switchable nanoprobe using TDNs as a scaffold. An RNA-hairpin sequence was linked to the terminal of one strand, and a photoinduced electron transfer pair (PET) was attached to the terminal of the complementary strand. The vicinity of them caused a fluorescent quenching, while the emergency of Ago2 and its corresponding siRNA could restore its fluorescence. Under conditions of inflammation, neurodegeneration and most diseases, abnormalities of hydrogen ions (H+ ) and superoxide anion (O2-) can be discovered. Li et al. incorporated hydroethidine (HE) and fluorescein (FAM) with the vertex of TDNs, the intensity of fluorescence would change in response to pH and O2−. Hence, a sensitive nanoprobe monitoring microenvironmental changes emerged for future disease diagnosis. The reason why TDNs was frequently employed as a bioimaging vehicle is that its rigid skeleton renders a fixed distance between fluorescent labels. It can prevent attached probes from self-quenching, and control their fluorescence recovery. In some cases, aptamer strand acts as not only a molecular recognition probe but also an activatable initiator. An electrochemical TDNs without additional reagent operated as follows: Once the target was captured by strand a and bounded with it, strand b on another vertex could pull them down through hybridization; the consequential collision of the terminal probe with electrode surface was induced, and eventually caused electron transfer. This linkage mechanism can be achieved in living animals, and thus expected to be applied in point-of care testing.

71In practice, bioimaging-related agents (e.g., 99mTc) are all candidates that could be integrated with TDNs. Indeed, multiple probes can be simultaneously functionalized for a more sensitive imaging nanodevice. Jiang et al. incorporated FA, radioisotope and ordinary label on TDNs with the linkage of multiple arms. A multimodality probe that can be observable under both near-infrared (NIR) and single-photon emission computed tomography (SPECT) was achieved.

72Beyond that, metallics and fluorophores were also commonly used in bioimaging and biosensing. A novel DNA nanoprobe containing AuNP, three Cyanine-5 (Cy5) and custom telomerase strand primer (TSP) was integrated for telomerase monitoring. Its fluorescence was quenched by fluorescence resonance energy transfer (FRET)-induced AuNP at an original state, which was regarded as “off”. After catching the signal of telomerase, hairpin structural TSP linked with AuNP would unfold, leading to the fluorescence recovery of Cy5 (“on” state). The sensitive detection of telomerase in cancer cells was a referable forebode in early diagnosis.

73In clinical, analysis of lymphonodi is essential in estimating oncology progress. Sentinel lymph nodes, the primary ones which malignant cells invade, become the emphasis of auxiliary examinations. However, case investigation reveals that patients with aggressive tumors like melanoma are susceptible to metastases after sentinel lymph nodes biopsy. Alternative noninvasive means are necessary. Dye-labeled TDNs with high in vivo stability, long circulation and great visualization was prepared, not only for lymph node imaging but also for tissues evaluation.

Cell surface engineering

74The cell surface membrane is the primary mediator for interactions of the cell-cell and the cell-microenvironment. Recently, the DNA nanomaterials were also investigated to modify the cell surface membrane for different aims, such as targeting, drug delivery, and enhanced interactions of cell-cell and cell-microenvironment. Gartner et al. have demonstrated that hybridization of complementary DNA sequences enabled the assembly of multicellular structures with defined cell-cell contacts. Akbari et al. also reported a DNA nanoplatform that could act as a membrane-bound breadboard (MBB) with nano-scale. This work developed a foundation to apply DNA nanomaterials as membrane engineering technologies, which could mimic and direct complex biomedical processes on the cell surface of different cells in tissues. Some DNA nanomaterials would be investigated for the cell surface engineering with some targeted aims, such as drug delivery and gene transduction. Furthermore, some DNA nanomaterials could combine with the proteins of cell membrane, and then could be internalizated by cells.Some studies have been deomenstrated that some DNA nanomaterials could transfer the cell membrane into the biomimic materials, which could act some functions in the palsma of the living cells.

75In the future studies, the membrane-bound DNA origami structures could enable programed assembly within the membrane to mimic functional biomolecular complexes, such as an immune synapse, especially given the wide use of DNA origami to template or organize proteins.

Summary and perspective

76In recent decades, DNA-based nanostructures have become one of the most attractive focuses because of their structural diversity and scientific values. As a basic component of living entities, DNA is endowed with excellent biocompatibility. Its 3D double-helix structure and small molecular weight confer variability and nanosized magnitude. As mentioned above, DNA nanoparticles can be assembled into arbitrary shapes including 2D triangle, rectangle, 3D polyhedron, liquid nanohydrogel, smarter nanocontainer and biomimetic constructions. More fancy structures might be available in the future.

77More importantly, DNA nanoparticles have showed influences on cell biological activities, especially on cell proliferation. Accordingly, their roles in tissue regeneration were broadly investigated in tissues including bone, cartilage, blood vessel, nerve, skeletal and cardiac muscles, skin and corneal systems. They also attract tremendous attentions when they serve as nanocarriers. Compared with traditional nanoparticles, they are more variform for the following reasons: (1) flexible joints because every strand of DNA-based nanostructures can be concatenated or linked with an extended arm; (2) abundant binding sites, as the assembly of DNA frameworks provides a hollow internal space for drug molecules; (3) negative charge, so that positive-charged substances can be integrated with them under electrostatic attraction. In this context, studies started applying them as nanoscale vehicles to transport various drugs into cellular focal sites for a desired efficacy. Therapeutical moieties with distinctive natures were chosen to incorporate with DNA nanoparticles. Aptamers (AS1411, MUC1, HApt, etc.) and antineoplastics (DOX, PTX, 5-FU, etc.) modified nanostructures were the most attractive. Their capabilities of antitumor effect, MDR reversion and photodynamic promotion were discovered. Then, the notion of multi-modality nanosystems were put forward to enhance their targeting performance. In addition, through the combination with immune agents (e.g., CpG) and fluorescent labels (e.g., FAM), DNA nanoparticles were also of great significance in immunostimulating, biosensing and bioimaging. More advanced nanotools with logic gates or structural switches were developed for further accurate administration.

78Although the biological applications of various DNA nanostructures were comprehensive and extensive, there remain some limitations to overcome, such as, the interaction mechanisms between DNA nanomaterials and cells, the short blood circulation time, and poor aggregation in target tissues. The cellular internalization processes of various DNA nanomaterials are the prerequisites for biological applications. For example, the TDNs have been widely investigated in bioimaging, drug delivery, targeted delivery of functional DNA or RNA sequence, and biocatalysis.,– Unlike ssDNA with poor cellular uptake properties, previous studies reported that TDNs could be internalized by cells without the assistance of transfection agents.– In the recent study, researcher combined drug affinity responsive target stability (DARTS) with liquid chromatography/tandem mass spectrometry (LC-MS/MS) techniques to explore the endocytosis process of TDNs. The study reported that the endocytosis of TDNs were related to caveolin-1 (CAV1) and micropinocytosis-related protein sorting nexin5 (SNX5). However, the cellular internalization processes of other DNA nanomaterials were not clear still now, which need more explorations.

79For the nature of DNA nanomaterials, different DNA nanomaterials encounter the challenges of poor blood circulation time and poor aggregation in target tissues. Some previous studies have demonstrated that the DNA nanomaterials (TDNs, HApt-TDNs, and DNA aptamer, etc) could circulate in body no >1 h, which were quickly eliminated by different cells and organs (such as macrophages, liver, and kidney) before DNA nanomaterials arriving at target tissues. Therefore, some other bionic materials were investigated to prolong the blood circulation time, such as liposomes and cell membranes. Some previous studies have reported various DNA-coated liposomes for drug delivery.– In a recent report, Han et al. found that tannic acid (TA) could mediate the co-assembly of branched-DNA/RNA and A549 lung cancer cell membrane-camouflaged to form nanocomplex (nanocomplex@A549m), which could strengthen the affinity between TA and nucleic acids/membrane proteins. The objectives of nanocomplex@A549m with the application of A549 lung cancer cell membrane-camouflaged were to prolong the blood circulation and reduce macrophage clearance. Moreover, the nanocomplex@A549m could effectively bind to target cells. From this study, we think that the cell membrane-camouflaged method (stem cells, cancer cells, blood cells, and exosomes, etc) might inspire other researchers to develop more DNA-based nanocomplex@cell-membrance materials., In further studies, DNA nanomaterials might be combine with other materials for more applications, such as hydrogel, nanozyme, and bimimic cell membrane nanomaterials.

80In conclusion, due to their structural flexibility, multiform customized DNA-based nanostructures were created. Some innovative creations discussed in this review provided valuable directions for the development of DNA-based nanostructures in biomedicine. Regarding the biological performance, acquired nanostructures were explored in tissue engineering and regeneration. As a high-efficient drug delivery system, they could be used as assembly templates to generate agent-modified nanodevices that execute rationally designed behaviors, including tumor therapy, MDR reversion, immunotherapy and biosensing. While studies and analyses were mostly conducted in vitro and the biological effects in different aspects are encouraging, in vivo studies are critical and needed to confirm the observed effects, assess the side effects and make the comprehensive evaluation before achieving the ultimate clinical application of DNA-based nanostructures.

References 526

1.
Dong Y, et al. DNA functional materials assembled from branched DNA: design, synthesis, and applications. Chem. Rev. 2020;120:9420-9481.
Not in our library10.1021/acs.chemrev.0c00294
2.
Broker TR, Lehman IR. Branched DNA molecules: intermediates in T4 recombination. J. Mol. Biol. 1971;60:131-149.
Not in our library10.1016/0022-2836(71)90453-0
3.
Seeman NC. DNA nanotechnology: from the pub to information-based chemistry. Methods Mol. Biol. 2018;1811:1-9.
Not in our library10.1007/978-1-4939-8582-1_1
4.
Seeman NC. DNA nanotechnology: novel DNA constructions. Annu. Rev. Biophys. Biomol. Struct. 1998;27:225-248.
Not in our library10.1146/annurev.biophys.27.1.225
5.
Seeman NC, Sleiman HF. DNA nanotechnology. Nat. Rev. Mater. 2018;3:17068.
Not in our library10.1038/natrevmats.2017.68
6.
Seeman NC. Nucleic-acid junctions and lattices. J. Theor. Biol. 1982;99:237-247.
Not in our library10.1016/0022-5193(82)90002-9
7.
Seeman NC. DNA engineering and its application to nanotechnology. Trends Biotechnol. 1999;17:437-443.
Not in our library10.1016/s0167-7799(99)01360-8
8.
Seeman NC, et al. Two dimensions and two States in DNA nanotechnology. J. Biomol. Struct. Dyn. 2000;17:253-262.
Not in our library10.1080/07391102.2000.10506629
9.
Seeman NC. Key experimental approaches in DNA nanotechnology. Curr. Protoc. Nucleic Acid Chem. 2002;Chapter 12:11.
Not in our library10.1002/0471142700.nc1201s09
10.
Fan S, et al. Create nanoscale patterns with DNA origami. Small. 2019;15:e1805554.
Not in our library10.1002/smll.201805554
11.
Jones MR, Seeman NC, Mirkin CA. Nanomaterials. programmable materials and the nature of the DNA bond. Science. 2015;347:1260901.
Not in our library10.1126/science.1260901
12.
Hu Y, Niemeyer CM. From DNA nanotechnology to material systems engineering. Adv. Mater. 2019;31:e1806294.
Not in our library10.1002/adma.201806294
13.
Chao J, et al. Solving mazes with single-molecule DNA navigators. Nat. Mater. 2019;18:273-279.
Not in our library10.1038/s41563-018-0205-3
14.
Harroun SG, et al. Programmable DNA switches and their applications. Nanoscale. 2018;10:4607-4641.
Not in our library10.1039/c7nr07348h
15.
Hu Y, Cecconello A, Idili A, Ricci F, Willner I. Triplex DNA nanostructures: from basic properties to applications. Angew. Chem. Int. Ed. Engl. 2017;56:15210-15233.
Not in our library10.1002/anie.201701868
16.
Seeman NC. DNA in a material world. Nature. 2003;421:427-431.
Not in our library10.1038/nature01406
17.
Jia S, et al. Programming DNA origami patterning with non-canonical DNA-based metallization reactions. Nat. Commun. 2019;10:5597.
Not in our library10.1038/s41467-019-13507-5
18.
Gopinath A, Miyazono E, Faraon A, Rothemund PW. Engineering and mapping nanocavity emission via precision placement of DNA origami. Nature. 2016;535:401-405.
Not in our library10.1038/nature18287
19.
Wing R, et al. Crystal structure analysis of a complete turn of B-DNA. Nature. 1980;287:755-758.
Not in our library10.1038/287755a0
20.
Franklin RE, Gosling RG. Molecular structure of nucleic acids. Molecular configuration in sodium thymonucleate. 1953. Ann. N. Y. Acad. Sci. 1995;758:16-17.
Not in our library
21.
Franklin RE, Gosling RG. Molecular configuration in sodium thymonucleate. Nature. 1953;171:740-741.
Not in our library10.1038/171740a0
22.
Wilkins MH, Stokes AR, Wilson HR. Molecular structure of nucleic acids. Molecular structure of deoxypentose nucleic acids. 1953. Ann. N. Y. Acad. Sci. 1995;758:13-16.
Not in our library10.1111/j.1749-6632.1995.tb24824.x
23.
Wilkins MH, Stokes AR, Wilson HR. Molecular structure of deoxypentose nucleic acids. Nature. 1953;171:738-740.
Not in our library10.1038/171738a0
24.
Watson JD, Crick FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171:737-738.
Not in our library10.1038/171737a0
25.
Mergny JL, Sen D. DNA quadruple helices in nanotechnology. Chem. Rev. 2019;119:6290-6325.
Not in our library10.1021/acs.chemrev.8b00629
26.
Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL. Polymorphism of DNA double helices. J. Mol. Biol. 1980;143:49-72.
Not in our library10.1016/0022-2836(80)90124-2
27.
Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ. Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies. J. Biomol. Struct. Dyn. 1988;6:299-309.
Not in our library10.1080/07391102.1988.10507714
28.
Structural diversity of supercoiled DNA · 2015
Corrected
29.
Zhang F, Nangreave J, Liu Y, Yan H. Structural DNA nanotechnology: state of the art and future perspective. J. Am. Chem. Soc. 2014;136:11198-11211.
Not in our library10.1021/ja505101a
30.
Fu J, Liu M, Liu Y, Yan H. Spatially-interactive biomolecular networks organized by nucleic acid nanostructures. Acc. Chem. Res. 2012;45:1215-1226.
Not in our library10.1021/ar200295q
31.
Alivisatos AP, et al. Organization of ‘nanocrystal molecules’ using DNA. Nature. 1996;382:609-611.
Not in our library10.1038/382609a0
32.
Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature. 1996;382:607-609.
Not in our library10.1038/382607a0
33.
Julin S, Nummelin S, Kostiainen MA, Linko V. DNA nanostructure-directed assembly of metal nanoparticle superlattices. J. Nanopart. Res.: Interdiscip. Forum Nanoscale Sci. Technol. 2018;20:119.
Not in our library10.1007/s11051-018-4225-3
34.
Aldaye FA, Palmer AL, Sleiman HF. Assembling materials with DNA as the guide. Science. 2008;321:1795-1799.
Not in our library10.1126/science.1154533
35.
Wang X, et al. Paranemic crossover DNA: there and back again. Chem. Rev. 2019;119:6273-6289.
Not in our library10.1021/acs.chemrev.8b00207
36.
Loescher S, Groeer S, Walther A. 3D DNA origami nanoparticles: from basic design principles to emerging applications in soft matter and (bio-)nanosciences. Angew. Chem. Int. Ed. Engl. 2018;57:10436-10448.
Not in our library10.1002/anie.201801700
37.
Hong F, Zhang F, Liu Y, Yan H. DNA origami: scaffolds for creating higher order structures. Chem. Rev. 2017;117:12584-12640.
Not in our library10.1021/acs.chemrev.6b00825
38.
Rothemund PW, Folding DNA. to create nanoscale shapes and patterns. Nature. 2006;440:297-302.
Not in our library10.1038/nature04586
39.
Torring T, Voigt NV, Nangreave J, Yan H, Gothelf KV. DNA origami: a quantum leap for self-assembly of complex structures. Chem. Soc. Rev. 2011;40:5636-5646.
Not in our library10.1039/c1cs15057j
40.
Petersen P, Tikhomirov G, Qian L. Information-based autonomous reconfiguration in systems of interacting DNA nanostructures. Nat. Commun. 2018;9:5362.
Not in our library10.1038/s41467-018-07805-7
41.
Wang SS, Ellington AD. Pattern generation with nucleic acid chemical reaction networks. Chem. Rev. 2019;119:6370-6383.
Not in our library10.1021/acs.chemrev.8b00625
42.
Simmel FC, Yurke B, Singh HR. Principles and applications of nucleic acid strand displacement reactions. Chem. Rev. 2019;119:6326-6369.
Not in our library10.1021/acs.chemrev.8b00580
43.
Thubagere AJ, et al. A cargo-sorting DNA robot. Science. 2017;357:eaan6558.
Not in our library10.1126/science.aan6558
44.
Zhang DY, Seelig G. Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 2011;3:103-113.
Not in our library10.1038/nchem.957
45.
Kopperger E, et al. A self-assembled nanoscale robotic arm controlled by electric fields. Science. 2018;359:296-301.
Not in our library10.1126/science.aao4284
46.
Hu Q, Li H, Wang L, Gu H, Fan C. DNA nanotechnology-enabled drug delivery systems. Chem. Rev. 2019;119:6459-6506.
Not in our library10.1021/acs.chemrev.7b00663
47.
Kohman RE, Kunjapur AM, Hysolli E, Wang Y, Church GM. From designing the molecules of life to designing life: future applications derived from advances in DNA technologies. Angew. Chem. Int. Ed. Engl. 2018;57:4313-4328.
Not in our library10.1002/anie.201707976
48.
Li J, Green AA, Yan H, Fan C. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nat. Chem. 2017;9:1056-1067.
Not in our library10.1038/nchem.2852
49.
Yang D, et al. DNA materials: bridging nanotechnology and biotechnology. Acc. Chem. Res. 2014;47:1902-1911.
Not in our library10.1021/ar5001082
50.
Zhang Y, et al. Programmable and multifunctional DNA-based materials for biomedical applications. Adv. Mater. 2018;30:e1703658.
Not in our library10.1002/adma.201703658
51.
Zhou L, et al. Functional DNA-based hydrogel intelligent materials for biomedical applications. J. Mater. Chem. B. 2020;8:1991-2009.
Not in our library10.1039/c9tb02716e
52.
Jiang Q, et al. Rationally designed DNA-based nanocarriers. Adv. Drug Deliv. Rev. 2019;147:2-21.
Not in our library10.1016/j.addr.2019.02.003
53.
Elfwing A, et al. DNA based hybrid material for interface engineering in polymer solar cells. ACS Appl. Mater. Interfaces. 2018;10:9579-9586.
Not in our library10.1021/acsami.7b17807
54.
Li J, et al. Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications. Chem. Soc. Rev. 2016;45:1410-1431.
Not in our library10.1039/c5cs00586h
55.
Maeda M, Kojima T, Song Y, Takayama S. DNA-based biomaterials for immunoengineering. Adv. Healthc. Mater. 2019;8:e1801243.
Not in our library10.1002/adhm.201801243
56.
Chandrasekaran AR, et al. DNA nanotechnology approaches for microRNA detection and diagnosis. Nucleic Acids Res. 2019;47:10489-10505.
Not in our library10.1093/nar/gkz580
57.
Roh YH, Ruiz RC, Peng S, Lee JB, Luo D. Engineering DNA-based functional materials. Chem. Soc. Rev. 2011;40:5730-5744.
Not in our library10.1039/c1cs15162b
58.
Khajouei S, Ravan H, Ebrahimi A. DNA hydrogel-empowered biosensing. Adv. Colloid Interface Sci. 2020;275:102060.
Not in our library10.1016/j.cis.2019.102060
59.
Li M, et al. Engineering multifunctional DNA hybrid nanospheres through coordination-driven self-assembly. Angew. Chem. Int. Ed. Engl. 2019;58:1350-1354.
Not in our library10.1002/anie.201810735
60.
Liu S, Jiang Q, Wang Y, Ding B. Biomedical applications of DNA-based molecular devices. Adv. Healthc. Mater. 2019;8:e1801658.
Not in our library10.1002/adhm.201801658
61.
Samanta A, Medintz IL. Nanoparticles and DNA-a powerful and growing functional combination in bionanotechnology. Nanoscale. 2016;8:9037-9095.
Not in our library10.1039/c5nr08465b
62.
Liu N, et al. Tetrahedral framework nucleic acids promote corneal epithelial wound healing in vitro and in vivo. Small. 2019;15:e1901907.
Not in our library10.1002/smll.201901907
63.
Ma W, et al. Self-assembled tetrahedral DNA nanostructures promote neural stem cell proliferation and neuronal differentiation. ACS Appl Mater. Interfaces. 2018;10:7892-7900.
Not in our library10.1021/acsami.8b00833
64.
Ma WJ, et al. Tetrahedral DNA nanostructures facilitate neural stem cell migration via activating RHOA/ROCK2 signalling pathway. Cell Prolif. 2018;51:e12503.
Not in our library10.1111/cpr.12503
65.
Shao X, et al. Tetrahedral DNA nanostructure: a potential promoter for cartilage tissue regeneration via regulating chondrocyte phenotype and proliferation. Small. 2017;13:1602770.
Not in our library10.1002/smll.201602770
66.
Shi S, et al. Self-assembled tetrahedral DNA nanostructures promote adipose-derived stem cell migration via lncRNA XLOC 010623 and RHOA/ROCK2 signal pathway. ACS Appl. Mater. Interfaces. 2016;8:19353-19363.
Not in our library10.1021/acsami.6b06528
67.
Shi SR, et al. Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes. Chem. Commun. 2018;54:1327-1330.
Not in our library10.1039/c7cc09397g
68.
Ma W, et al. An intelligent DNA nanorobot with in vitro enhanced protein lysosomal degradation of HER2. Nano Lett. 2019;19:4505-4517.
Not in our library10.1021/acs.nanolett.9b01320
69.
Lee H, Dam DH, Ha JW, Yue J, Odom TW. Enhanced human epidermal growth factor receptor 2 degradation in breast cancer cells by lysosome-targeting gold nanoconstructs. ACS Nano. 2015;9:9859-9867.
Not in our library10.1021/acsnano.5b05138
70.
Petrizzo A, et al. Functional characterization of biodegradable nanoparticles as antigen delivery system. J. Exp. Clin. Cancer Res. 2015;34:114.
Not in our library10.1186/s13046-015-0231-9
71.
Liu B, et al. DNA-origami-based assembly of anisotropic plasmonic gold nanostructures. Small. 2017;13:1603991.
Not in our library10.1002/smll.201603991
72.
Edwardson TG, Lau KL, Bousmail D, Serpell CJ, Sleiman HF. Transfer of molecular recognition information from DNA nanostructures to gold nanoparticles. Nat. Chem. 2016;8:162-170.
Not in our library10.1038/nchem.2420
73.
Utsuno K, Uludag H. Thermodynamics of polyethylenimine-DNA binding and DNA condensation. Biophys. J. 2010;99:201-207.
Not in our library10.1016/j.bpj.2010.04.016
74.
Zhang Y, et al. Ionic-crosslinked polysaccharide/PEI/DNA nanoparticles for stabilized gene delivery. Carbohydr. Polym. 2018;201:246-256.
Not in our library10.1016/j.carbpol.2018.08.063
75.
Xie L, Ding X, Budry R, Mao G. Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery. Int. J. Nanomed. 2018;13:4943-4960.
Not in our library10.2147/ijn.s162353
76.
Ewe A, et al. Storage stability of optimal liposome-polyethylenimine complexes (lipopolyplexes) for DNA or siRNA delivery. Acta Biomaterialia. 2014;10:2663-2673.
Not in our library10.1016/j.actbio.2014.02.037
77.
Tian TR, et al. Synthesis of an ethyleneimine/tetrahedral DNA nanostructure complex and its potential application as a multi-functional delivery vehicle. Nanoscale. 2017;9:18402-18412.
Not in our library10.1039/c7nr07130b
78.
Liu W, et al. An investigation on the physicochemical properties of chitosan/DNA polyelectrolyte complexes. Biomaterials. 2005;26:2705-2711.
Not in our library10.1016/j.biomaterials.2004.07.038
79.
Gu T, Wang J, Xia H, Wang S, Yu X. Direct electrochemistry and electrocatalysis of horseradish peroxidase immobilized in a DNA/chitosan-Fe(3)O(4) magnetic nanoparticle bio-complex film. Materials. 2014;7:1069-1083.
Not in our library10.3390/ma7021069
80.
Kumar S, et al. Enhanced chitosan-DNA interaction by 2-acrylamido-2-methylpropane coupling for an efficient transfection in cancer cells. J. Mater. Chem. B. 2015;3:3465-3475.
Not in our library10.1039/c4tb02070g
81.
Walsh DP, et al. Bioinspired star-shaped poly(l-lysine) polypeptides: efficient polymeric nanocarriers for the delivery of DNA to mesenchymal stem cells. Mol. Pharm. 2018;15:1878-1891.
Not in our library10.1021/acs.molpharmaceut.8b00044
82.
Boylan NJ, et al. Enhancement of airway gene transfer by DNA nanoparticles using a pH-responsive block copolymer of polyethylene glycol and poly-L-lysine. Biomaterials. 2012;33:2361-2371.
Not in our library10.1016/j.biomaterials.2011.11.080
83.
von Erlach T, et al. Formation and characterization of DNA-polymer-condensates based on poly(2-methyl-2-oxazoline) grafted poly(L-lysine) for non-viral delivery of therapeutic DNA. Biomaterials. 2011;32:5291-5303.
Not in our library10.1016/j.biomaterials.2011.03.080
84.
Chen T, Romesberg FE. Enzymatic synthesis, amplification, and application of dna with a functionalized backbone. Angew. Chem. Int. Ed. Engl. 2017;56:14046-14051.
Not in our library10.1002/anie.201707367
85.
Zhan Y, et al. Diversity of DNA nanostructures and applications in oncotherapy. Biotechnol. J. 2020;15:e1900094.
Not in our library10.1002/biot.201900094
86.
Schnitzbauer J, Strauss MT, Schlichthaerle T, Schueder F, Jungmann R. Super-resolution microscopy with DNA-PAINT. Nat. Protoc. 2017;12:1198-1228.
Not in our library10.1038/nprot.2017.024
87.
Ngo TA, et al. Protein adaptors assemble functional proteins on DNA scaffolds. Chem. Commun. (Camb.). 2019;55:12428-12446.
Not in our library10.1039/c9cc04661e
88.
Zhan Y, et al. DNA-Based nanomedicine with targeting and enhancement of therapeutic efficacy of breast cancer cells. ACS Appl. Mater. Interfaces. 2019;11:15354-15365.
Not in our library10.1021/acsami.9b03449
89.
Wang M, et al. Near-infrared light-activated DNA-agonist nanodevice for nongenetically and remotely controlled cellular signaling and behaviors in live animals. Nano Lett. 2019;19:2603-2613.
Not in our library10.1021/acs.nanolett.9b00421
90.
Taniguchi J, et al. A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm. Nucleic Acids Res. 2017;45:9219-9228.
Not in our library10.1093/nar/gkx693
91.
Hendrikson WJ, et al. Biological and tribological assessment of poly(ethylene oxide terephthalate)/poly(butylene terephthalate), polycaprolactone, and poly (L\DL) lactic acid plotted scaffolds for skeletal tissue regeneration. Adv. Healthc. Mater. 2016;5:232-243.
Not in our library10.1002/adhm.201500067
92.
Jayme CC, et al. DNA polymeric films as a support for cell growth as a new material for regenerative medicine: compatibility and applicability. Exp. Cell Res. 2017;360:404-412.
Not in our library10.1016/j.yexcr.2017.09.033
93.
Basu S, et al. Harnessing the noncovalent interactions of DNA backbone with 2D silicate nanodisks to fabricate injectable therapeutic hydrogels. ACS Nano. 2018;12:9866-9880.
Not in our library10.1021/acsnano.8b02434
94.
Feng G, et al. Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration. Biomaterials. 2017;131:86-97.
Not in our library10.1016/j.biomaterials.2017.03.029
95.
Zhang Y, et al. Nucleic acids and analogs for bone regeneration. Bone Res. 2018;6:37.
Not in our library10.1038/s41413-018-0042-7
96.
Mahlknecht G, Sela M, Yarden Y. Aptamer targeting the ERBB2 receptor tyrosine kinase for applications in tumor therapy. Methods Mol. Biol. 2015;1317:3-15.
Not in our library10.1007/978-1-4939-2727-2_1
97.
Yu X, et al. Targeting EGFR/HER2/HER3 with a three-in-one aptamer-siRNA chimera confers superior activity against HER2( +) breast cancer. Mol. Ther. Nucleic Acids. 2018;10:317-330.
Not in our library10.1016/j.omtn.2017.12.015
98.
Bai S, et al. High-discrimination factor nanosensor based on tetrahedral dna nanostructures and gold nanoparticles for detection of MiRNA-21 in live cells. Theranostics. 2018;8:2424-2434.
Not in our library10.7150/thno.23852
99.
Zeng D, et al. DNA tetrahedral nanostructure-based electrochemical miRNA biosensor for simultaneous detection of multiple miRNAs in pancreatic carcinoma. ACS Appl. Mater. Interfaces. 2017;9:24118-24125.
Not in our library10.1021/acsami.7b05981
100.
Li Q, et al. Aptamer-modified tetrahedral DNA nanostructure for tumor-targeted drug delivery. ACS Appl. Mater. Interfaces. 2017;9:36695-36701.
Not in our library10.1021/acsami.7b13328
101.
Wang L, Arrabito G. Hybrid, multiplexed, functional DNA nanotechnology for bioanalysis. Analyst. 2015;140:5821-5848.
Not in our library10.1039/c5an00861a
102.
Li C, et al. A writable polypeptide-DNA hydrogel with rationally designed multi-modification sites. Small. 2015;11:1138-1143.
Not in our library10.1002/smll.201401906
103.
Estrich NA, Hernandez-Garcia A, de Vries R, LaBean TH. Engineered diblock polypeptides improve DNA and gold solubility during molecular assembly. ACS Nano. 2017;11:831-842.
Not in our library10.1021/acsnano.6b07291
104.
Nakata E, Dinh H, Nguyen TM, Morii T. DNA binding adaptors to assemble proteins of interest on DNA scaffold. Methods Enzymol. 2019;617:287-322.
Not in our library10.1016/bs.mie.2018.12.014
105.
Chandrasekaran AR. Programmable DNA scaffolds for spatially-ordered protein assembly. Nanoscale. 2016;8:4436-4446.
Not in our library10.1039/c5nr08685j
106.
Chandler M, et al. Breaking and joining single-stranded DNA: the HUH endonuclease superfamily. Nat. Rev. Microbiol. 2013;11:525-538.
Not in our library10.1038/nrmicro3067
107.
Xie X, et al. Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures. Nanoscale. 2018;10:5457-5465.
Not in our library10.1039/c7nr09692e
108.
Halley PD, et al. Daunorubicin-loaded DNA origami nanostructures circumvent drug-resistance mechanisms in a leukemia model. Small. 2016;12:308-320.
Not in our library10.1002/smll.201502118
109.
Kim KR, et al. Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells. Chem. Commun. (Camb.). 2013;49:2010-2012.
Not in our library10.1039/c3cc38693g
110.
Liu M, et al. Aptamer-targeted DNA nanostructures with doxorubicin to treat protein tyrosine kinase 7-positive tumours. Cell Prolif. 2018;52:e12511.
Not in our library10.1111/cpr.12511
111.
Meng L, et al. Tetrahedral DNA nanostructure-delivered DNAzyme for gene silencing to suppress cell growth. ACS Appl. Mater. Interfaces. 2019;11:6850-6857.
Not in our library10.1021/acsami.8b22444
112.
Samanta A, Banerjee S, Liu Y. DNA nanotechnology for nanophotonic applications. Nanoscale. 2015;7:2210-2220.
Not in our library10.1039/c4nr06283c
113.
Wang ZG, Song C, Ding B. Functional DNA nanostructures for photonic and biomedical applications. Small. 2013;9:2210-2222.
Not in our library10.1002/smll.201300141
114.
Shen B, Kostiainen MA, Linko V. DNA origami nanophotonics and plasmonics at interfaces. Langmuir. 2018;34:14911-14920.
Not in our library10.1021/acs.langmuir.8b01843
115.
Maune HT, et al. Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates. Nat. Nanotechnol. 2010;5:61-66.
Not in our library10.1038/nnano.2009.311
116.
Amodio A, Del Grosso E, Troina A, Placidi E, Ricci F. Remote electronic control of DNA-based reactions and nanostructure assembly. Nano Lett. 2018;18:2918-2923.
Not in our library10.1021/acs.nanolett.8b00179
117.
Gates EP, Dearden AM, Woolley AT. DNA-templated lithography and nanofabrication for the fabrication of nanoscale electronic circuitry. Crit. Rev. Anal. Chem. 2014;44:354-370.
Not in our library10.1080/10408347.2014.910636
118.
Yang YR, Liu Y, Yan H. DNA nanostructures as programmable biomolecular scaffolds. Bioconjug. Chem. 2015;26:1381-1395.
Not in our library10.1021/acs.bioconjchem.5b00194
119.
Manipulating Enzymes Properties with DNA Nanostructures · 2019
Not checked
120.
Winfree E, Liu FR, Wenzler LA, Seeman NC. Design and self-assembly of two-dimensional DNA crystals. Nature. 1998;394:539-544.
Not in our library10.1038/28998
121.
Yan H, Zhang XP, Shen ZY, Seeman NC. A robust DNA mechanical device controlled by hybridization topology. Nature. 2002;415:62-65.
Not in our library10.1038/415062a
122.
Chen JH, Seeman NC. Synthesis from DNA of a molecule with the connectivity of a cube. Nature. 1991;350:631-633.
Not in our library10.1038/350631a0
123.
Liu WY, Zhong H, Wang RS, Seeman NC. Crystalline two-dimensional DNA-origami arrays. Angew. Chem. Int Ed. 2011;50:264-267.
Not in our library10.1002/anie.201005911
124.
Le JD, et al. DNA-templated self-assembly of metallic nanocomponent arrays on a surface. Nano Lett. 2004;4:2343-2347.
Not in our library10.1021/nl048635+
125.
Selmi DN, et al. DNA-templated protein arrays for single-molecule imaging. Nano Lett. 2011;11:657-660.
Not in our library10.1021/nl1037769
126.
Holthausen JT, Wyman C, Kanaar R. Regulation of DNA strand exchange in homologous recombination. DNA Repair. 2010;9:1264-1272.
Not in our library10.1016/j.dnarep.2010.09.014
127.
Wang X, Seeman NC. Assembly and characterization of 8-arm and 12-arm DNA branched junctions. J. Am. Chem. Soc. 2007;129:8169-8176.
Not in our library10.1021/ja0693441
128.
Wang YL, Mueller JE, Kemper B, Seeman NC. Assembly and characterization of five-arm and six-arm DNA branched junctions. Biochemistry. 1991;30:5667-5674.
Not in our library10.1021/bi00237a005
129.
Kallenbach NR, Ma RI, Seeman NC. An immobile nucleic-acid junction constructed from oligonucleotides. Nature. 1983;305:829-831.
Not in our library10.1038/305829a0
130.
Sa-Ardyen P, Vologodskii AV, Seeman NC. The flexibility of DNA double crossover molecules. Biophys. J. 2003;84:3829-3837.
Not in our library10.1016/s0006-3495(03)75110-8
131.
Fu TJ, Seeman NC. DNA double-crossover molecules. Biochemistry. 1993;32:3211-3220.
Not in our library10.1021/bi00064a003
132.
Winfree E, Liu F, Wenzler LA, Seeman NC. Design and self-assembly of two-dimensional DNA crystals. Nature. 1998;394:539-544.
Not in our library10.1038/28998
133.
Yan H, Park SH, Finkelstein G, Reif JH, LaBean TH. DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science. 2003;301:1882-1884.
Not in our library10.1126/science.1089389
134.
He Y, Chen Y, Liu H, Ribbe AE, Mao C. Self-assembly of hexagonal DNA two-dimensional (2D) arrays. J. Am. Chem. Soc. 2005;127:12202-12203.
Not in our library10.1021/ja0541938
135.
Mathieu F, et al. Six-helix bundles designed from DNA. Nano Lett. 2005;5:661-665.
Not in our library10.1021/nl050084f
136.
He Y, Tian Y, Ribbe AE, Mao C. Highly connected two-dimensional crystals of DNA six-point-stars. J. Am. Chem. Soc. 2006;128:15978-15979.
Not in our library10.1021/ja0665141
137.
Lin C, Liu Y, Rinker S, Yan H. DNA tile based self-assembly: building complex nanoarchitectures. Chemphyschem. 2006;7:1641-1647.
Not in our library10.1002/cphc.200600260
138.
Zheng J, et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal. Nature. 2009;461:74-77.
Not in our library10.1038/nature08274
139.
Yan H, LaBean TH, Feng LP, Reif JH. Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proc. Natl Acad. Sci. USA. 2003;100:8103-8108.
Not in our library10.1073/pnas.1032954100
140.
Shih WM, Quispe JD, Joyce GF. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature. 2004;427:618-621.
Not in our library10.1038/nature02307
141.
Qian L, et al. Analogic China map constructed by DNA. Chin. Sci. Bull. 2006;51:2973-2976.
Not in our library10.1007/s11434-006-2223-9
142.
Andersen ES, et al. DNA origami design of dolphin-shaped structures with flexible tails. ACS Nano. 2008;2:1213-1218.
Not in our library10.1021/nn800215j
143.
Han DR, et al. DNA origami with complex curvatures in three-dimensional space. Science. 2011;332:342-346.
Not in our library10.1126/science.1202998
144.
Yan H, LaBean TH, Feng L, Reif JH. Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices. Proc. Natl Acad. Sci. USA. 2003;100:8103-8108.
Not in our library10.1073/pnas.1032954100
145.
Andersen ES, et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature. 2009;459:73-76.
Not in our library10.1038/nature07971
146.
Zadegan RM, et al. Construction of a 4 zeptoliters switchable 3D DNA box origami. ACS Nano. 2012;6:10050-10053.
Not in our library10.1021/nn303767b
147.
Zadegan RM, Jepsen MDE, Hildebrandt LL, Birkedal V, Kjems J. Construction of a fuzzy and boolean logic gates based on DNA. Small. 2015;11:1811-1817.
Not in our library10.1002/smll.201402755
148.
Kuzuya A, Komiyama M. Design and construction of a box-shaped 3D-DNA origami. Chem. Commun. (Camb.). 2009;28:4182-4184.
Not in our library10.1039/b907800b
149.
Endo M, Hidaka K, Kato T, Namba K, Sugiyama H. DNA prism structures constructed by folding of multiple rectangular arms. J. Am. Chem. Soc. 2009;131:15570-15571.
Not in our library10.1021/ja904252e
150.
Douglas SM, Chou JJ, Shih WM. DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc. Natl Acad. Sci. USA. 2007;104:6644-6648.
Not in our library10.1073/pnas.0700930104
151.
Han D, et al. DNA origami with complex curvatures in three-dimensional space. Science. 2011;332:342-346.
Not in our library10.1126/science.1202998
152.
Pound E, Ashton JR, Becerril HA, Woolley AT. Polymerase chain reaction based scaffold preparation for the production of thin, branched DNA origami nanostructures of arbitrary sizes. Nano Lett. 2009;9:4302-4305.
Not in our library10.1021/nl902535q
153.
Han D, et al. DNA gridiron nanostructures based on four-arm junctions. Science. 2013;339:1412-1415.
Not in our library10.1126/science.1232252
154.
Zhang F, et al. Complex wireframe DNA origami nanostructures with multi-arm junction vertices. Nat. Nanotechnol. 2015;10:779-+.
Not in our library10.1038/nnano.2015.162
155.
Veneziano R, et al. DNA NANOTECHNOLOGY Designer nanoscale DNA assemblies programmed from the top down. Science. 2016;352:1534.
Not in our library10.1126/science.aaf4388
156.
Benson E, et al. DNA rendering of polyhedral meshes at the nanoscale. Nature. 2015;523:441-444.
Not in our library10.1038/nature14586
157.
Benson E, et al. Computer-aided production of scaffolded DNA nanostructures from flat sheet meshes. Angew. Chem. Int. Ed. Engl. 2016;55:8869-8872.
Not in our library10.1002/anie.201602446
158.
Ellis-Monaghan JA, McDowell A, Moffatt I, Pangborn G. DNA origami and the complexity of Eulerian circuits with turning costs. Nat. Comput. 2015;14:491-503.
Not in our library10.1007/s11047-014-9457-2
159.
Matthies M, Agarwal NP, Schmidt TL. Design and synthesis of triangulated DNA origami trusses. Nano Lett. 2016;16:2108-2113.
Not in our library10.1021/acs.nanolett.6b00381
160.
Mallik L, et al. Electron microscopic visualization of protein assemblies on flattened DNA origami. ACS Nano. 2015;9:7133-7141.
Not in our library10.1021/acsnano.5b01841
161.
Wu N, et al. Molecular threading and tunable molecular recognition on DNA origami nanostructures. J. Am. Chem. Soc. 2013;135:12172-12175.
Not in our library10.1021/ja403863a
162.
Douglas SM, et al. Self-assembly of DNA into nanoscale three-dimensional shapes (vol 459, pg 414, 2009). Nature. 2009;459:1154-1154.
Not in our library10.1038/nature08165
163.
Ke YG, et al. Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 2009;131:15903-15908.
Not in our library10.1021/ja906381y
164.
Ke YG, Voigt NV, Gothelf KV, Shih WM. Multilayer DNA origami packed on hexagonal and hybrid lattices. J. Am. Chem. Soc. 2012;134:1770-1774.
Not in our library10.1021/ja209719k
165.
Dietz H, Douglas SM, Shih WM. Folding DNA into twisted and curved nanoscale shapes. Science. 2009;325:725-730.
Not in our library10.1126/science.1174251
166.
Liedl T, Hogberg B, Tytell J, Ingber DE, Shih WM. Self-assembly of three-dimensional prestressed tensegrity structures from DNA. Nat. Nanotechnol. 2010;5:520-524.
Not in our library10.1038/nnano.2010.107
167.
Ke Y, Bellot G, Voigt NV, Fradkov E, Shih WM. Two design strategies for enhancement of multilayer-DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning. Chem. Sci. 2012;3:2587-2597.
Not in our library10.1039/c2sc20446k
168.
Hong F, Jiang S, Wang T, Liu Y, Yan H. 3D framework DNA origami with layered crossovers. Angew. Chem. Int. Ed. Engl. 2016;55:12832-12835.
Not in our library10.1002/anie.201607050
169.
Douglas SM, et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 2009;37:5001-5006.
Not in our library10.1093/nar/gkp436
170.
Catherinot V, Labesse G. ViTO: tool for refinement of protein sequence-structure alignments. Bioinformatics. 2004;20:3694-3696.
Not in our library10.1093/bioinformatics/bth429
171.
Bai XC, Martin TG, Scheres SH, Dietz H. Cryo-EM structure of a 3D DNA-origami object. Proc. Natl Acad. Sci. USA. 2012;109:20012-20017.
Not in our library10.1073/pnas.1215713109
172.
Fischer S, et al. Shape and interhelical spacing of dna origami nanostructures studied by small-angle x-ray scattering. Nano Lett. 2016;16:4282-4287.
Not in our library10.1021/acs.nanolett.6b01335
173.
Wagenbauer KF, Wachauf CH, Dietz H. Quantifying quality in DNA self-assembly. Nat. Commun. 2014;5:3691.
Not in our library10.1038/ncomms4691
174.
Brown S, et al. An easy-to-prepare mini-scaffold for DNA origami. Nanoscale. 2015;7:16621-16624.
Not in our library10.1039/c5nr04921k
175.
Nickels PC, et al. DNA origami structures directly assembled from intact bacteriophages. Small. 2014;10:1765-1769.
Not in our library10.1002/smll.201303442
176.
Kick B, Praetorius F, Dietz H, Weuster-Botz D. Efficient production of single-stranded phage DNA as scaffolds for DNA origami. Nano Lett. 2015;15:4672-4676.
Not in our library10.1021/acs.nanolett.5b01461
177.
Kick B, Hensler S, Praetorius F, Dietz H, Weuster-Botz D. Specific growth rate and multiplicity of infection affect high-cell-density fermentation with bacteriophage M13 for ssDNA production. Biotechnol. Bioeng. 2017;114:777-784.
Not in our library10.1002/bit.26200
178.
Said H, et al. M1.3–a small scaffold for DNA origami. Nanoscale. 2013;5:284-290.
Not in our library10.1039/c2nr32393a
179.
Martin TG, Dietz H. Magnesium-free self-assembly of multi-layer DNA objects. Nat. Commun. 2012;3:1103.
Not in our library10.1038/ncomms2095
180.
Zhang Z, Song J, Besenbacher F, Dong M, Gothelf KV. Self-assembly of DNA origami and single-stranded tile structures at room temperature. Angew. Chem. Int. Ed. Engl. 2013;52:9219-9223.
Not in our library10.1002/anie.201303611
181.
Kopielski A, Schneider A, Csaki A, Fritzsche W. Isothermal DNA origami folding: avoiding denaturing conditions for one-pot, hybrid-component annealing. Nanoscale. 2015;7:2102-2106.
Not in our library10.1039/c4nr04176c
182.
Timm C, Niemeyer CM. Assembly and purification of enzyme-functionalized DNA origami structures. Angew. Chem. Int. Ed. Engl. 2015;54:6745-6750.
Not in our library10.1002/anie.201500175
183.
Shaw A, Benson E, Hogberg B. Purification of functionalized DNA origami nanostructures. ACS Nano. 2015;9:4968-4975.
Not in our library10.1021/nn507035g
184.
Stahl E, Martin TG, Praetorius F, Dietz H. Facile and scalable preparation of pure and dense DNA origami solutions. Angew. Chem. Int. Ed. Engl. 2014;53:12735-12740.
Not in our library10.1002/anie.201405991
185.
Bellot G, McClintock MA, Lin C, Shih WM. Recovery of intact DNA nanostructures after agarose gel-based separation. Nat. Methods. 2011;8:192-194.
Not in our library10.1038/nmeth0311-192
186.
Lin C, Perrault SD, Kwak M, Graf F, Shih WM. Purification of DNA-origami nanostructures by rate-zonal centrifugation. Nucleic Acids Res. 2013;41:e40.
Not in our library10.1093/nar/gks1070
187.
Rajendran A, Endo M, Katsuda Y, Hidaka K, Sugiyama H. Photo-cross-linking-assisted thermal stability of DNA origami structures and its application for higher-temperature self-assembly. J. Am. Chem. Soc. 2011;133:14488-14491.
Not in our library10.1021/ja204546h
188.
Hofr C, Brabec V. Thermal and thermodynamic properties of duplex DNA containing site-specific interstrand cross-link of antitumor cisplatin or its clinically ineffective trans isomer. J. Biol. Chem. 2001;276:9655-9661.
Not in our library10.1074/jbc.m010205200
189.
Eskelinen AP, Rosilo H, Kuzyk A, Torma P, Kostiainen MA. Controlling the formation of DNA origami structures with external signals. Small. 2012;8:2016-2020.
Not in our library10.1002/smll.201102697
190.
Browne WR, Feringa BL. Making molecular machines work. Nat. Nanotechnol. 2006;1:25-35.
Not in our library10.1038/nnano.2006.45
191.
Li SL, et al. New light on the ring-chain equilibrium of a hydrogen-bonded supramolecular polymer based on a photochromic dithienylethene unit and its energy-transfer properties as a storage material. Chem.-Eur. J. 2011;17:10716-10723.
Not in our library10.1002/chem.201100691
192.
ten Brinke G, Ruokolainen J, Ikkala O. Supramolecular materials based on hydrogen-bonded polymers. Adv. Polym. Sci. 2007;207:113-177.
Not in our library10.1007/12_2006_111
193.
Stuart MA, et al. Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 2010;9:101-113.
Not in our library10.1038/nmat2614
194.
Gallego I, Grover MA, Hud NV. Folding and imaging of DNA nanostructures in anhydrous and hydrated deep-eutectic solvents. Angew. Chem. Int. Ed. Engl. 2015;54:6765-6769.
Not in our library10.1002/anie.201412354
195.
Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu. Rev. Chem. Biomolecular Eng. 2011;2:403-430.
Not in our library10.1146/annurev-chembioeng-061010-114257
196.
Orlando G, et al. Regenerative medicine and organ transplantation: past, present, and future. Transplantation. 2011;91:1310-1317.
Not in our library10.1097/tp.0b013e318219ebb5
197.
Song HG, Rumma RT, Ozaki CK, Edelman ER, Chen CS. Vascular tissue engineering: progress, challenges, and clinical promise. Cell Stem Cell. 2018;22:340-354.
Not in our library10.1016/j.stem.2018.02.009
198.
Tarassoli SP, et al. Skin tissue engineering using 3D bioprinting: an evolving research field. J. Plast. Reconstr. Aesthet. Surg. 2018;71:615-623.
Not in our library10.1016/j.bjps.2017.12.006
199.
Yu JR, et al. Current and future perspectives on skin tissue engineering: key features of biomedical research, translational assessment, and clinical application. Adv. Healthc. Mater. 2019;8:e1801471.
Not in our library10.1002/adhm.201801471
200.
Jana S, Levengood SK, Zhang M. Anisotropic materials for skeletal-muscle-tissue engineering. Adv. Mater. 2016;28:10588-10612.
Not in our library10.1002/adma.201600240
201.
Hassanzadeh P, Atyabi F, Dinarvand R. Tissue engineering: Still facing a long way ahead. J. Control. Release. 2018;279:181-197.
Not in our library10.1016/j.jconrel.2018.04.024
202.
Polacheck WJ, Kutys ML, Tefft JB, Chen CS. Microfabricated blood vessels for modeling the vascular transport barrier. Nat. Protoc. 2019;14:1425-1454.
Not in our library10.1038/s41596-019-0144-8
203.
Wang Y, et al. Engineering vascular tissue with functional smooth muscle cells derived from human iPS cells and nanofibrous scaffolds. Biomaterials. 2014;35:8960-8969.
Not in our library10.1016/j.biomaterials.2014.07.011
204.
Impact of Age on Human Adipose Stem Cells for Bone Tissue Engineering · 2017
Not checked
205.
Ho-Shui-Ling A, et al. Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials. 2018;180:143-162.
Not in our library10.1016/j.biomaterials.2018.07.017
206.
Kwee BJ, Mooney DJ. Biomaterials for skeletal muscle tissue engineering. Curr. Opin. Biotechnol. 2017;47:16-22.
Not in our library10.1016/j.copbio.2017.05.003
207.
Aamodt JM, Grainger DW. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials. 2016;86:68-82.
Not in our library10.1016/j.biomaterials.2016.02.003
208.
Shih YV, Varghese S. Tissue engineered bone mimetics to study bone disorders ex vivo: role of bioinspired materials. Biomaterials. 2019;198:107-121.
Not in our library10.1016/j.biomaterials.2018.06.005
209.
Saldin LT, Cramer MC, Velankar SS, White LJ, Badylak SF. Extracellular matrix hydrogels from decellularized tissues: Structure and function. Acta Biomaterialia. 2017;49:1-15.
Not in our library10.1016/j.actbio.2016.11.068
210.
Keane TJ, Swinehart IT, Badylak SF. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance. Methods. 2015;84:25-34.
Not in our library10.1016/j.ymeth.2015.03.005
211.
Lancaster MA, et al. Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 2017;35:659-666.
Not in our library10.1038/nbt.3906
212.
Kang HW, et al. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat. Biotechnol. 2016;34:312-319.
Not in our library10.1038/nbt.3413
213.
Takebe T, Zhang B, Radisic M. Synergistic engineering: organoids meet organs-on-a-chip. Cell Stem Cell. 2017;21:297-300.
Not in our library10.1016/j.stem.2017.08.016
214.
Wubneh A, Tsekoura EK, Ayranci C, Uludag H. Current state of fabrication technologies and materials for bone tissue engineering. Acta Biomaterialia. 2018;80:1-30.
Not in our library10.1016/j.actbio.2018.09.031
215.
Atasoy-Zeybek A, Kose GT. Gene therapy strategies in bone tissue engineering and current clinical applications. Adv. Exp. Med. Biol. 2018;1119:85-101.
Not in our library10.1007/5584_2018_253
216.
Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920-926.
Not in our library10.1126/science.8493529
217.
Salvay DM, Shea LD. Inductive tissue engineering with protein and DNA-releasing scaffolds. Mol. Biosyst. 2006;2:36-48.
Not in our library10.1039/b514174p
218.
Wobus AM, Boheler KR. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol. Rev. 2005;85:635-678.
Not in our library10.1152/physrev.00054.2003
219.
Guan K, Schmidt MM, Ding Q, Chang H, Wobus AM. Embryonic stem cells in vitro-prospects for cell and developmental biology, embryotoxicology and cell therapy. Altex. 1999;16:135-141.
Not in our library
220.
Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005;19:1129-1155.
Not in our library10.1101/gad.1303605
221.
Hersel U, Dahmen C, Kessler H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials. 2003;24:4385-4415.
Not in our library10.1016/s0142-9612(03)00343-0
222.
Arnold MS, Guler MO, Hersam MC, Stupp SI. Encapsulation of carbon nanotubes by self-assembling peptide amphiphiles. Langmuir. 2005;21:4705-4709.
Not in our library10.1021/la0469452
223.
Zhang S, et al. Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials. 1995;16:1385-1393.
Not in our library10.1016/0142-9612(95)96874-y
224.
Vasita R, Katti DS. Nanofibers and their applications in tissue engineering. Int. J. Nanomed. 2006;1:15-30.
Not in our library10.2147/nano.2006.1.1.15
225.
Murphy WL, Mooney DJ. Controlled delivery of inductive proteins, plasmid DNA and cells from tissue engineering matrices. J. Periodontal Res. 1999;34:413-419.
Not in our library10.1111/j.1600-0765.1999.tb02275.x
226.
Jang JH, Bengali Z, Houchin TL, Shea LD. Surface adsorption of DNA to tissue engineering scaffolds for efficient gene delivery. J. Biomed. Mater. Res. Part A. 2006;77:50-58.
Not in our library10.1002/jbm.a.30643
227.
Zhou M, et al. Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic differentiation of dental pulp stem cells via activation of the notch signaling pathway. Nanomedicine. 2018;14:1227-1236.
Not in our library10.1016/j.nano.2018.02.004
228.
Gonzalez-Fernandez T, et al. Pore-forming bioinks to enable spatio-temporally defined gene delivery in bioprinted tissues. J. Control. Release. 2019;301:13-27.
Not in our library10.1016/j.jconrel.2019.03.006
229.
Walsh DP, et al. Transfection of autologous host cells in vivo using gene activated collagen scaffolds incorporating star-polypeptides. J. Control. Release. 2019;304:191-203.
Not in our library10.1016/j.jconrel.2019.05.009
230.
Ma W, et al. Enhanced neural regeneration with a concomitant treatment of framework nucleic acid and stem cells in spinal cord injury. ACS Appl. Mater. Interfaces. 2020;12:2095-2106.
Not in our library10.1021/acsami.9b19079
231.
Zhu J, et al. Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway. Signal Transduct. Target. Ther. 2020;5:120.
Not in our library10.1038/s41392-020-0173-3
232.
Li W, et al. A gene-activating skin substitute comprising PLLA/POSS nanofibers and plasmid DNA encoding ANG and bFGF promotes in vivo revascularization and epidermalization. J. Mater. Chem. B. 2018;6:6977-6992.
Not in our library10.1039/c8tb02006j
233.
Duman N, et al. Topical folinic acid enhances wound healing in rat model. Adv. Med. Sci. 2018;63:347-352.
Not in our library10.1016/j.advms.2018.04.011
234.
Eke G, Mangir N, Hasirci N, MacNeil S, Hasirci V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials. 2017;129:188-198.
Not in our library10.1016/j.biomaterials.2017.03.021
235.
Milan PB, et al. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells. Acta Biomaterialia. 2016;45:234-246.
Not in our library10.1016/j.actbio.2016.08.053
236.
Bhowmick S, Scharnweber D, Koul V. Co-cultivation of keratinocyte-human mesenchymal stem cell (hMSC) on sericin loaded electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) stimulates epithelial differentiation in hMSCs: In vitro study. Biomaterials. 2016;88:83-96.
Not in our library10.1016/j.biomaterials.2016.02.034
237.
Keil TWM, Baldassi D, Merkel OM. T-cell targeted pulmonary siRNA delivery for the treatment of asthma. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2020;12:e1634.
Not in our library10.1002/wnan.1634
238.
Liang H, et al. Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys. Sci. Adv. 2020;6:eabb5274.
Not in our library10.1126/sciadv.abb5274
239.
Mao C, et al. The clearance effect of tetrahedral DNA nanostructures on senescent human dermal fibroblasts. ACS Appl. Mater. Interfaces. 2019;11:1942-1950.
Not in our library10.1021/acsami.8b20530
240.
Shao XR, et al. Neuroprotective effect of tetrahedral DNA nanostructures in a cell model of Alzheimer’s disease. ACS Appl. Mater. Interfaces. 2018;10:23682-23692.
Not in our library10.1021/acsami.8b07827
241.
Whittlesey KJ, Shea LD. Delivery systems for small molecule drugs, proteins, and DNA: the neuroscience/biomaterial interface. Exp. Neurol. 2004;190:1-16.
Not in our library10.1016/j.expneurol.2004.06.020
242.
Pannier AK, Shea LD. Controlled release systems for DNA delivery. Mol. Ther. 2004;10:19-26.
Not in our library10.1016/j.ymthe.2004.03.020
243.
Amani A, Kabiri T, Shafiee S, Hamidi A. Preparation and characterization of PLA-PEG-PLA/PEI/DNA nanoparticles for improvement of transfection efficiency and controlled release of DNA in gene delivery systems. Iran. J. Pharm. Res.: IJPR. 2019;18:125-141.
Not in our library
244.
Gajbhiye KR, Chaudhari BP, Pokharkar VB, Pawar A, Gajbhiye V. Stimuli-responsive biodegradable polyurethane nano-constructs as a potential triggered drug delivery vehicle for cancer therapy. Int. J. Pharm. 2020;588:119781.
Not in our library10.1016/j.ijpharm.2020.119781
245.
Hashemi M, Shamshiri A, Saeedi M, Tayebi L, Yazdian-Robati R. Aptamer-conjugated PLGA nanoparticles for delivery and imaging of cancer therapeutic drugs. Arch. Biochem. Biophys. 2020;691:108485.
Not in our library10.1016/j.abb.2020.108485
246.
Wolski P, Nieszporek K, Panczyk AT. Carbon nanotubes and short cytosine-rich telomeric DNA oligomeres as platforms for controlled release of doxorubicin-a molecular dynamics study. Int. J. Mol. Sci. 2020;21:3619.
Not in our library10.3390/ijms21103619
247.
Tan X, Jia F, Wang P, Zhang K. Nucleic acid-based drug delivery strategies. J. Control. Release. 2020;323:240-252.
Not in our library10.1016/j.jconrel.2020.03.040
248.
Peng Q, et al. Understanding the biomedical effects of the self-assembled tetrahedral DNA nanostructure on living cells. ACS Appl. Mater. Interfaces. 2016;8:12733-12739.
Not in our library10.1021/acsami.6b03786
249.
Faingold A, Cohen SR, Reznikov N, Wagner HD. Osteonal lamellae elementary units: lamellar microstructure, curvature and mechanical properties. Acta Biomaterialia. 2013;9:5956-5962.
Not in our library10.1016/j.actbio.2012.11.032
250.
Raftery RM, et al. Delivering nucleic-acid based nanomedicines on biomaterial scaffolds for orthopedic tissue repair: challenges, progress and future perspectives. Adv. Mater. 2016;28:5447-5469.
Not in our library10.1002/adma.201505088
251.
Betz VM, et al. Recent advances in gene-enhanced bone tissue engineering. J. Gene Med. 2018;20:e3018.
Not in our library10.1002/jgm.3018
252.
Balmayor ER, Evans CH. RNA therapeutics for tissue engineering. Tissue Eng. Part A. 2019;25:9-11.
Not in our library10.1089/ten.tea.2018.0315
253.
Shim MS, Kwon YJ. Controlled cytoplasmic and nuclear localization of plasmid DNA and siRNA by differentially tailored polyethylenimine. J. Control. Release. 2009;133:206-213.
Not in our library10.1016/j.jconrel.2008.10.007
254.
Khorsand B, et al. Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model. J. Control. Release. 2017;248:53-59.
Not in our library10.1016/j.jconrel.2017.01.008
255.
Kim TH, Singh RK, Kang MS, Kim JH, Kim HW. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration. Nanoscale. 2016;8:8300-8311.
Not in our library10.1039/c5nr07933k
256.
Schlickewei C, et al. A bioactive nano-calcium phosphate paste for in-situ transfection of BMP-7 and VEGF-A in a rabbit critical-size bone defect: results of an in vivo study. J. Mater. Sci. Mater. Med. 2019;30:15.
Not in our library10.1007/s10856-019-6217-y
257.
Takanche JS, et al. Chitosan-gold nanoparticles mediated gene delivery of c-myb facilitates osseointegration of dental implants in ovariectomized rat. Artif. Cells Nanomed. Biotechnol. 2018;46:S807-S817.
Not in our library10.1080/21691401.2018.1513940
258.
Huang M, et al. Comparison of osteogenic differentiation induced by siNoggin and pBMP-2 delivered by lipopolysaccharide-amine nanopolymersomes and underlying molecular mechanisms. Int. J. Nanomed. 2019;14:4229-4245.
Not in our library10.2147/ijn.s203540
259.
Liang D, et al. In vitro non-viral gene delivery with nanofibrous scaffolds. Nucleic Acids Res. 2005;33:e170.
Not in our library10.1093/nar/gni171
260.
Li Y, Liu C. Nanomaterial-based bone regeneration. Nanoscale. 2017;9:4862-4874.
Not in our library10.1039/c7nr00835j
261.
Wang SJ, et al. Biomimetic nanosilica-collagen scaffolds for in situ bone regeneration: toward a cell-free, one-step surgery. Adv. Mater. 2019;31:e1904341.
Not in our library10.1002/adma.201904341
262.
Li G, Zhou T, Lin S, Shi S, Lin Y. Nanomaterials for craniofacial and dental tissue engineering. J. Dent. Res. 2017;96:725-732.
Not in our library10.1177/0022034517706678
263.
Mohammadi M, et al. Micro and nanotechnologies for bone regeneration: Recent advances and emerging designs. J. Control. Release. 2018;274:35-55.
Not in our library10.1016/j.jconrel.2018.01.032
264.
Lv L, et al. The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation. Biomaterials. 2015;39:193-205.
Not in our library10.1016/j.biomaterials.2014.11.002
265.
D’Mello S, et al. Bone regeneration using gene-activated matrices. AAPS J. 2017;19:43-53.
Not in our library10.1208/s12248-016-9982-2
266.
Tierney EG, Duffy GP, Hibbitts AJ, Cryan SA, O’Brien FJ. The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds. J. Control. Release. 2012;158:304-311.
Not in our library10.1016/j.jconrel.2011.11.026
267.
Shimer AL, Oner FC, Vaccaro AR. Spinal reconstruction and bone morphogenetic proteins: open questions. Injury. 2009;40:S32-S38.
Not in our library10.1016/s0020-1383(09)70009-9
268.
Winn SR, Hu Y, Sfeir C, Hollinger JO. Gene therapy approaches for modulating bone regeneration. Adv. Drug Deliv. Rev. 2000;42:121-138.
Not in our library10.1016/s0169-409x(00)00057-0
269.
Chan HL, McCauley LK. Parathyroid hormone applications in the craniofacial skeleton. J. Dent. Res. 2013;92:18-25.
Not in our library10.1177/0022034512464779
270.
Elangovan S, et al. Chemically modified RNA activated matrices enhance bone regeneration. J. Control. Release. 2015;218:22-28.
Not in our library10.1016/j.jconrel.2015.09.050
271.
Higashi T, et al. Novel lipidated sorbitol-based molecular transporters for non-viral gene delivery. J. Control. Release. 2009;136:140-147.
Not in our library10.1016/j.jconrel.2009.01.024
272.
des Rieux A, Shikanov A, Shea LD. Fibrin hydrogels for non-viral vector delivery in vitro. J. Control. Release. 2009;136:148-154.
Not in our library10.1016/j.jconrel.2009.02.004
273.
Lei Y, Rahim M, Ng Q, Segura T. Hyaluronic acid and fibrin hydrogels with concentrated DNA/PEI polyplexes for local gene delivery. J. Control. Release. 2011;153:255-261.
Not in our library10.1016/j.jconrel.2011.01.028
274.
Togashi R, et al. A hepatic pDNA delivery system based on an intracellular environment sensitive vitamin E-scaffold lipid-like material with the aid of an anti-inflammatory drug. J. Control. Release. 2018;279:262-270.
Not in our library10.1016/j.jconrel.2018.04.022
275.
Siegman S, Truong NF, Segura T. Encapsulation of PEGylated low-molecular-weight PEI polyplexes in hyaluronic acid hydrogels reduces aggregation. Acta Biomaterialia. 2015;28:45-54.
Not in our library10.1016/j.actbio.2015.09.020
276.
Nie H, Soh BW, Fu YC, Wang CH. Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnol. Bioeng. 2008;99:223-234.
Not in our library10.1002/bit.21517
277.
Nie H, Wang CH. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J. Control. Release. 2007;120:111-121.
Not in our library10.1016/j.jconrel.2007.03.018
278.
Fu YC, Nie H, Ho ML, Wang CK, Wang CH. Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol. Bioeng. 2008;99:996-1006.
Not in our library10.1002/bit.21648
279.
Nie H, Ho ML, Wang CK, Wang CH, Fu YC. BMP-2 plasmid loaded PLGA/HAp composite scaffolds for treatment of bone defects in nude mice. Biomaterials. 2009;30:892-901.
Not in our library10.1016/j.biomaterials.2008.10.029
280.
Keeney M, et al. Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model. J. Biomed. Mater. Res. Part A. 2016;104:2099-2107.
Not in our library10.1002/jbm.a.35735
281.
Atluri K, Seabold D, Hong L, Elangovan S, Salem AK. Nanoplex-mediated codelivery of fibroblast growth factor and bone morphogenetic protein genes promotes osteogenesis in human adipocyte-derived mesenchymal stem cells. Mol. Pharm. 2015;12:3032-3042.
Not in our library10.1021/acs.molpharmaceut.5b00297
282.
Elangovan S, et al. The enhancement of bone regeneration by gene activated matrix encoding for platelet derived growth factor. Biomaterials. 2014;35:737-747.
Not in our library10.1016/j.biomaterials.2013.10.021
283.
Qiao C, et al. Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo. Int. J. Nanomed. 2013;8:2985-2995.
Not in our library10.2147/ijn.s45184
284.
Qiao C, et al. Sustained release poly (lactic-co-glycolic acid) microspheres of bone morphogenetic protein 2 plasmid/calcium phosphate to promote in vitro bone formation and in vivo ectopic osteogenesis. Am. J. Transl. Res. 2015;7:2561-2572.
Not in our library
285.
Hadjicharalambous C, Kozlova D, Sokolova V, Epple M, Chatzinikolaidou M. Calcium phosphate nanoparticles carrying BMP-7 plasmid DNA induce an osteogenic response in MC3T3-E1 pre-osteoblasts. J. Biomed. Mater. Res. Part A. 2015;103:3834-3842.
Not in our library10.1002/jbm.a.35527
286.
Bhattarai G, Lee YH, Lee MH, Yi HK. Gene delivery of c-myb increases bone formation surrounding oral implants. J. Dent. Res. 2013;92:840-845.
Not in our library10.1177/0022034513497753
287.
Li DD, et al. Characterization and cytocompatibility of thermosensitive hydrogel embedded with chitosan nanoparticles for delivery of bone morphogenetic protein-2 plasmid DNA. J. Mater. Sci. Mater. Med. 2016;27:134.
Not in our library10.1007/s10856-016-5743-0
288.
Li H, et al. Accelerated bony defect healing based on chitosan thermosensitive hydrogel scaffolds embedded with chitosan nanoparticles for the delivery of BMP2 plasmid DNA. J. Biomed. Mater. Res. Part A. 2017;105:265-273.
Not in our library10.1002/jbm.a.35900
289.
Supper S, et al. Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications. Expert Opin. drug Deliv. 2014;11:249-267.
Not in our library10.1517/17425247.2014.867326
290.
Carballo-Pedrares N, Fuentes-Boquete I, Diaz-Prado S, Rey-Rico A. hydrogel-based localized nonviral gene delivery in regenerative medicine approaches-an overview. Pharmaceutics. 2020;12:752.
Not in our library10.3390/pharmaceutics12080752
291.
Lauritano D, Limongelli L, Moreo G, Favia G, Carinci F. Nanomaterials for periodontal tissue engineering: chitosan-based scaffolds. a systematic review. Nanomaterials. 2020;10:605.
Not in our library10.3390/nano10040605
292.
Wu S, et al. Evaluation of chitosan hydrogel for sustained delivery of VEGF for odontogenic differentiation of dental pulp stem cells. Stem Cells Int. 2019;2019:1515040.
Not in our library10.1155/2019/1515040
293.
Walsh DP, et al. Bioinspired star-shaped poly(L-lysine) polypeptides: efficient polymeric nanocarriers for the delivery of dna to mesenchymal stem cells. Mol. Pharm. 2018;15:1878-1891.
Not in our library10.1021/acs.molpharmaceut.8b00044
294.
Shinozaki Y, et al. Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an adult rat calvarial defect model. J. Biomed. Mater. Res. Part B, Appl. Biomater. 2014;102:1669-1676.
Not in our library10.1002/jbm.b.33143
295.
Toda M, Ohno J, Shinozaki Y, Ozaki M, Fukushima T. Osteogenic potential for replacing cells in rat cranial defects implanted with a DNA/protamine complex paste. Bone. 2014;67:237-245.
Not in our library10.1016/j.bone.2014.07.018
296.
Charles LF, et al. Effects of low dose FGF-2 and BMP-2 on healing of calvarial defects in old mice. Exp. Gerontol. 2015;64:62-69.
Not in our library10.1016/j.exger.2015.02.006
297.
Shi S, et al. Modulation of chondrocyte motility by tetrahedral DNA nanostructures. Cell Prolif. 2017;50:e12368.
Not in our library10.1111/cpr.12368
298.
Shi S, et al. Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes. Chem. Commun. (Camb.). 2018;54:1327-1330.
Not in our library10.1039/c7cc09397g
299.
Shao XR, et al. Effect of tetrahedral DNA nanostructures on osteogenic differentiation of mesenchymal stem cells via activation of the Wnt/beta-catenin signaling pathway. Nanomedicine. 2017;13:1809-1819.
Not in our library10.1016/j.nano.2017.02.011
300.
Zhou M, et al. Effect of tetrahedral DNA nanostructures on proliferation and osteogenic differentiation of human periodontal ligament stem cells. Cell Prolif. 2019;52:e12566.
Not in our library10.1111/cpr.12566
301.
Zhou M, et al. The protective effect of tetrahedral framework nucleic acids on periodontium under inflammatory conditions. Bioact. Mater. 2021;6:1676-1688.
Not in our library10.1016/j.bioactmat.2020.11.018
302.
Sirong S, et al. Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis. Bone Res. 2020;8:6.
Not in our library10.1038/s41413-019-0077-4
303.
Wang G, et al. Evaluation of the protective effect of a prime-boost strategy with plasmid DNA followed by recombinant adenovirus expressing BmAMA1 as vaccines against Babesia microti infection in hamster. Acta Parasitol. 2018;63:368-374.
Not in our library10.1515/ap-2018-0042
304.
Burger C, Chu B. Functional nanofibrous scaffolds for bone reconstruction. Colloids Surf. B Biointerfaces. 2007;56:134-141.
Not in our library10.1016/j.colsurfb.2006.09.023
305.
Gunatillake PA, Adhikari R. Biodegradable synthetic polymers for tissue engineering. Eur. Cells Mater. 2003;5:1-16.
Not in our library10.22203/ecm.v005a01
306.
Wang MO, et al. Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering. Adv. Mater. 2015;27:138-144.
Not in our library10.1002/adma.201403943
307.
O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater. Today. 2011;14:88-95.
Not in our library10.1016/s1369-7021(11)70058-x
308.
Meinel L, Kaplan DL. Silk constructs for delivery of musculoskeletal therapeutics. Adv. Drug Deliv. Rev. 2012;64:1111-1122.
Not in our library10.1016/j.addr.2012.03.016
309.
Raftery RM, et al. Delivering nucleic-acid based nanomedicines on biomaterial scaffolds for orthopedic tissue repair: challenges, progress and future. Perspectives. 2016;28:5447-5469.
Not in our library10.1002/adma.201505088
310.
Chirico G, Pallavicini P, Collini M. Gold nanostars for superficial diseases: a promising tool for localized hyperthermia? Nanomedicine (Lond.). 2014;9:1-3.
Not in our library10.2217/nnm.13.186
311.
Endocytosis of Nanomedicines: The Case of Glycopeptide Engineered PLGA Nanoparticles · 2015
Not checked
312.
Katav T, et al. Modified pectin-based carrier for gene delivery: cellular barriers in gene delivery course. J. Control. Release. 2008;130:183-191.
Not in our library10.1016/j.jconrel.2008.06.002
313.
Jeong GW, Nah JW. Evaluation of disulfide bond-conjugated LMWSC-g-bPEI as non-viral vector for low cytotoxicity and efficient gene delivery. Carbohydr. Polym. 2017;178:322-330.
Not in our library10.1016/j.carbpol.2017.09.048
314.
Singh J, Michel D, Chitanda JM, Verrall RE, Badea I. Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles. J. Nanobiotechnol. 2012;10:7.
Not in our library10.1186/1477-3155-10-7
315.
Zhang B, Mallapragada S. The mechanism of selective transfection mediated by pentablock copolymers; part II: nuclear entry and endosomal escape. Acta Biomaterialia. 2011;7:1580-1587.
Not in our library10.1016/j.actbio.2010.11.033
316.
Wang J, Dou B, Bao Y. Efficient targeted pDNA/siRNA delivery with folate-low-molecular-weight polyethyleneimine-modified pullulan as non-viral carrier. Mater. Sci. Eng. C. Mater. Biol. Appl. 2014;34:98-109.
Not in our library10.1016/j.msec.2013.08.035
317.
Gu X, Ding F, Williams DF. Neural tissue engineering options for peripheral nerve regeneration. Biomaterials. 2014;35:6143-6156.
Not in our library10.1016/j.biomaterials.2014.04.064
318.
Chooi WH, Chew SY. Modulation of cell-cell interactions for neural tissue engineering: Potential therapeutic applications of cell adhesion molecules in nerve regeneration. Biomaterials. 2019;197:327-344.
Not in our library10.1016/j.biomaterials.2019.01.030
319.
Madigan NN, McMahon S, O’Brien T, Yaszemski MJ, Windebank AJ. Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds. Respir. Physiol. Neurobiol. 2009;169:183-199.
Not in our library10.1016/j.resp.2009.08.015
320.
Editorial. Engineering approaches to enhance neural tissue regeneration. Exp. Neurol. 319, 112873 (2019).
Not in our library10.1016/j.expneurol.2019.01.001
321.
Koss KM, Unsworth LD. Neural tissue engineering: bioresponsive nanoscaffolds using engineered self-assembling peptides. Acta Biomaterialia. 2016;44:2-15.
Not in our library10.1016/j.actbio.2016.08.026
322.
Tang X, et al. Bridging peripheral nerve defects with a tissue engineered nerve graft composed of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold. Biomaterials. 2012;33:3860-3867.
Not in our library10.1016/j.biomaterials.2012.02.008
323.
Yang S, et al. Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration. Theranostics. 2020;10:8227-8249.
Not in our library10.7150/thno.44276
324.
Willerth SM, Sakiyama-Elbert SE. Approaches to neural tissue engineering using scaffolds for drug delivery. Adv. Drug Deliv. Rev. 2007;59:325-338.
Not in our library10.1016/j.addr.2007.03.014
325.
Yao Y, et al. Efect of longitudinally oriented collagen conduit combined with nerve growth factor on nerve regeneration after dog sciatic nerve injury. J. Biomed. Mater. Res. Part B, Appl. Biomater. 2018;106:2131-2139.
Not in our library10.1002/jbm.b.34020
326.
Baiguera S, et al. Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering. Biomaterials. 2014;35:1205-1214.
Not in our library10.1016/j.biomaterials.2013.10.060
327.
Liang Y, Walczak P, Bulte JW. The survival of engrafted neural stem cells within hyaluronic acid hydrogels. Biomaterials. 2013;34:5521-5529.
Not in our library10.1016/j.biomaterials.2013.03.095
328.
Sufan W, et al. Sciatic nerve regeneration through alginate with tubulation or nontubulation repair in cat. J. Neurotrauma. 2001;18:329-338.
Not in our library10.1089/08977150151070991
329.
Chong EJ, et al. Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomaterialia. 2007;3:321-330.
Not in our library10.1016/j.actbio.2007.01.002
330.
Cui W, et al. Neuroprotective and neurotherapeutic effects of tetrahedral framework nucleic acids on Parkinson’s disease in vitro. ACS Appl. Mater. Interfaces. 2019;11:32787-32797.
Not in our library10.1021/acsami.9b10308
331.
Li J, et al. Ternary polyplex micelles with PEG shells and intermediate barrier to complexed DNA cores for efficient systemic gene delivery. J. Control. Release. 2015;209:77-87.
Not in our library10.1016/j.jconrel.2015.04.024
332.
Feng G, et al. Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas. Biomaterials. 2015;52:1-13.
Not in our library10.1016/j.biomaterials.2015.02.024
333.
Houchin-Ray T, Swift LA, Jang JH, Shea LD. Patterned PLG substrates for localized DNA delivery and directed neurite extension. Biomaterials. 2007;28:2603-2611.
Not in our library10.1016/j.biomaterials.2007.01.042
334.
Li J, Zha Z, Ge Z. Thermo-responsive polyplex micelles with PEG shells and PNIPAM layer to protect DNA cores for systemic gene therapy. Methods Mol. Biol. 2016;1445:269-276.
Not in our library10.1007/978-1-4939-3718-9_17
335.
Arkenbout EK, et al. Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice. Circulation. 2002;106:1530-1535.
Not in our library10.1161/01.cir.0000028811.03056.bf
336.
Pires NM, et al. Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation. Circulation. 2007;115:493-500.
Not in our library10.1161/circulationaha.106.626838
337.
Fassett MS, Jiang W, D’Alise AM, Mathis D, Benoist C. Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion. Proc. Natl Acad. Sci. USA. 2012;109:3891-3896.
Not in our library10.1073/pnas.1200090109
338.
Hanna RN, et al. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat. Immunol. 2011;12:778-785.
Not in our library10.1038/ni.2063
339.
Maxwell MA, et al. Nur77 regulates lipolysis in skeletal muscle cells. Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway. J. Biol. Chem. 2005;280:12573-12584.
Not in our library10.1074/jbc.m409580200
340.
Myers SA, Eriksson N, Burow R, Wang SC, Muscat GE. Beta-adrenergic signaling regulates NR4A nuclear receptor and metabolic gene expression in multiple tissues. Mol. Cell. Endocrinol. 2009;309:101-108.
Not in our library10.1016/j.mce.2009.05.006
341.
Pei L, et al. NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat. Med. 2006;12:1048-1055.
Not in our library10.1038/nm1471
342.
Taniguchi J, et al. A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm. Nucleic Acids Res. 2017;45:9219-9228.
Not in our library10.1093/nar/gkx693
343.
Wang L, et al. Imaging of Neurite Network with an Anti-L1CAM Aptamer Generated by Neurite-SELEX. J. Am. Chem. Soc. 2018;140:18066-18073.
Not in our library10.1021/jacs.8b10783
344.
Shah B, Yin PT, Ghoshal S, Lee KB. Multimodal magnetic core-shell nanoparticles for effective stem-cell differentiation and imaging. Angew. Chem. Int. Ed. Engl. 2013;52:6190-6195.
Not in our library10.1002/anie.201302245
345.
Shan J, Tenhu H. Recent advances in polymer protected gold nanoparticles: synthesis, properties and applications. Chem. Commun. (Camb.). 2007;28:4580-4598.
Not in our library10.1039/b707740h
346.
Ghosh Chaudhuri R, Paria S. Core/shell nanoparticles: classes, properties, synthesis mechanisms, characterization, and applications. Chem. Rev. 2012;112:2373-2433.
Not in our library10.1021/cr100449n
347.
Balasubramanian B, et al. Synthesis of monodisperse TiO2-paraffin core-shell nanoparticles for improved dielectric properties. ACS Nano. 2010;4:1893-1900.
Not in our library10.1021/nn9016422
348.
Zhang H, Lee MY, Hogg MG, Dordick JS, Sharfstein ST. Gene delivery in three-dimensional cell cultures by superparamagnetic nanoparticles. ACS Nano. 2010;4:4733-4743.
Not in our library10.1021/nn9018812
349.
Shao X, et al. Treatment of Alzheimer’s disease with framework nucleic acids. Cell Prolif. 2020;53:e12787.
Not in our library10.1111/cpr.12787
350.
Wackerhage H, Del Re,DP, Judson RN, Sudol M, Sadoshima J. The Hippo signal transduction network in skeletal and cardiac muscle. Sci. Signal. 2014;7:re4.
Not in our library10.1126/scisignal.2005096
351.
Lin KC, et al. Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation. Nat. Cell Biol. 2017;19:996-1002.
Not in our library10.1038/ncb3581
352.
Xin M, Olson EN, Bassel-Duby R. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nat. Rev. Mol. Cell Biol. 2013;14:529-541.
Not in our library10.1038/nrm3619
353.
Addis RC, Epstein JA. Induced regeneration–the progress and promise of direct reprogramming for heart repair. Nat. Med. 2013;19:829-836.
Not in our library10.1038/nm.3225
354.
Qian L, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012;485:593-598.
Not in our library10.1038/nature11044
355.
Collins CA, et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;122:289-301.
Not in our library10.1016/j.cell.2005.05.010
356.
Intrinsic and extrinsic mechanisms regulating satellite cell function · 2015
No notice
357.
Day K, Shefer G, Richardson JB, Enikolopov G, Yablonka-Reuveni Z. Nestin-GFP reporter expression defines the quiescent state of skeletal muscle satellite cells. Dev. Biol. 2007;304:246-259.
Not in our library10.1016/j.ydbio.2006.12.026
358.
Neural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function · 2020
No notice
359.
Qazi TH, Mooney DJ, Pumberger M, Geissler S, Duda GN. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. Biomaterials. 2015;53:502-521.
Not in our library10.1016/j.biomaterials.2015.02.110
360.
Del Carmen Ortuno-Costela M, Garcia-Lopez M, Cerrada V, Gallardo ME. iPSCs: a powerful tool for skeletal muscle tissue engineering. J. Cell. Mol. Med. 2019;23:3784-3794.
Not in our library10.1111/jcmm.14292
361.
Singh VK, Kumar N, Kalsan M, Saini A, Chandra R. Mechanism of induction: induced pluripotent stem cells (iPSCs). J. Stem Cells. 2015;10:43-62.
Not in our library
362.
Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation · 2018
Not checked
363.
Beldjilali-Labro M, et al. Biomaterials in tendon and skeletal muscle tissue engineering: current trends and challenges. Materials. 2018;11:4580-98.
Not in our library10.3390/ma11071116
364.
Blumenfeld CM, et al. Drug capture materials based on genomic DNA-functionalized magnetic nanoparticles. Nat. Commun. 2018;9:2870.
Not in our library10.1038/s41467-018-05305-2
365.
Ueki R, et al. A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application. Sci. Adv. 2020;6:eaay2801.
Not in our library10.1126/sciadv.aay2801
366.
Zhang M, et al. Cardioprotection of tetrahedral DNA nanostructures in myocardial ischemia-reperfusion injury. ACS Appl. Mater. interfaces. 2019;11:30631-30639.
Not in our library10.1021/acsami.9b10645
367.
The Nrf-2/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases · 2020
No notice
368.
Shen Y, Liu X, Shi J, Wu X. Involvement of Nrf2 in myocardial ischemia and reperfusion injury. Int. J. Biol. Macromol. 2019;125:496-502.
Not in our library10.1016/j.ijbiomac.2018.11.190
369.
Seifert AW, et al. Skin shedding and tissue regeneration in African spiny mice (Acomys). Nature. 2012;489:561-565.
Not in our library10.1038/nature11499
370.
Metcalfe AD, Ferguson MW. Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J. R. Soc. Interface. 2007;4:413-437.
Not in our library10.1098/rsif.2006.0179
371.
Fuchs E. Epithelial skin biology: three decades of developmental biology, a hundred questions answered and a thousand new ones to address. Curr. Top. Dev. Biol. 2016;116:357-374.
Not in our library10.1016/bs.ctdb.2015.11.033
372.
Roger M, et al. Bioengineering the microanatomy of human skin. J. Anat. 2019;234:438-455.
Not in our library10.1111/joa.12942
373.
Driskell RR, et al. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 2013;504:277-281.
Not in our library10.1038/nature12783
374.
Kim BS, Gao G, Kim JY, Cho DW. 3D cell printing of perfusable vascularized human skin equivalent composed of epidermis, dermis, and hypodermis for better structural recapitulation of native skin. Adv. Healthc. Mater. 2019;8:e1801019.
Not in our library10.1002/adhm.201801019
375.
Jiang Y, Lu S. Three-dimensional insights into dermal tissue as a cue for cellular behavior. Burns. 2014;40:191-199.
Not in our library10.1016/j.burns.2013.09.015
376.
Hurtley S, Hines PJ, Mueller KL, Culotta E. Skin. From bench to bedside. Introduction. Science. 2014;346:932-933.
Not in our library10.1126/science.346.6212.932
377.
Khavkin J, Ellis DA. Aging skin: histology, physiology, and pathology. Facial Plast. Surg. Clin. North Am. 2011;19:229-234.
Not in our library10.1016/j.fsc.2011.04.003
378.
Parna E, Aluoja A, Kingo K. Quality of life and emotional state in chronic skin disease. Acta Derm. Venereol. 2015;95:312-316.
Not in our library10.2340/00015555-1920
379.
Mendes AL, Miot HA, Haddad VJ. Diabetes mellitus and the skin. . Bras. Dermatol. 2017;92:8-20.
Not in our library10.1590/abd1806-4841.20175514
380.
Robinson KP, Chan JJ. Colchicine in dermatology: a review. Australas. J. Dermatol. 2018;59:278-285.
Not in our library10.1111/ajd.12795
381.
Morton LM, Phillips TJ. Wound healing and treating wounds: differential diagnosis and evaluation of chronic wounds. J. Am. Acad. Dermatol. 2016;74:589-605.
Not in our library10.1016/j.jaad.2015.08.068
382.
Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration · 2020
No notice
383.
Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration: current status and advances. Biomaterials. 2019;216:119267.
Not in our library10.1016/j.biomaterials.2019.119267
384.
Wang C, et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics. 2019;9:65-76.
Not in our library10.7150/thno.29766
385.
Chouhan D, Mandal BB. Silk biomaterials in wound healing and skin regeneration therapeutics: from bench to bedside. Acta Biomaterialia. 2020;103:24-51.
Not in our library10.1016/j.actbio.2019.11.050
386.
Sapru S, Das S, Mandal M, Ghosh AK, Kundu SC. Prospects of nonmulberry silk protein sericin-based nanofibrous matrices for wound healing-In vitro and in vivo investigations. Acta Biomaterialia. 2018;78:137-150.
Not in our library10.1016/j.actbio.2018.07.047
387.
Chouhan D, et al. Recombinant spider silk functionalized silkworm silk matrices as potential bioactive wound dressings and skin grafts. ACS Appl. Mater. Interfaces. 2018;10:23560-23572.
Not in our library10.1021/acsami.8b05853
388.
Guo R, Xu S, Ma L, Huang A, Gao C. The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen-chitosan dermal equivalents. Biomaterials. 2011;32:1019-1031.
Not in our library10.1016/j.biomaterials.2010.08.087
389.
Guo R, Xu S, Ma L, Huang A, Gao C. Enhanced angiogenesis of gene-activated dermal equivalent for treatment of full thickness incisional wounds in a porcine model. Biomaterials. 2010;31:7308-7320.
Not in our library10.1016/j.biomaterials.2010.06.013
390.
Yang Y, et al. Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats. Mol. Pharm. 2012;9:48-58.
Not in our library10.1021/mp200246b
391.
Lou D, Luo Y, Pang Q, Tan WQ, Ma L. Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis. Bioact. Mater. 2020;5:667-679.
Not in our library10.1016/j.bioactmat.2020.04.018
392.
Bao P, et al. The role of vascular endothelial growth factor in wound healing. J. Surg. Res. 2009;153:347-358.
Not in our library10.1016/j.jss.2008.04.023
393.
Wang P, et al. In situ formed anti-inflammatory hydrogel loading plasmid DNA encoding VEGF for burn wound healing. Acta Biomaterialia. 2019;100:191-201.
Not in our library10.1016/j.actbio.2019.10.004
394.
Yang Y, et al. Promotion of skin regeneration in diabetic rats by electrospun core-sheath fibers loaded with basic fibroblast growth factor. Biomaterials. 2011;32:4243-4254.
Not in our library10.1016/j.biomaterials.2011.02.042
395.
He S, et al. Multiple release of polyplexes of plasmids VEGF and bFGF from electrospun fibrous scaffolds towards regeneration of mature blood vessels. Acta Biomaterialia. 2012;8:2659-2669.
Not in our library10.1016/j.actbio.2012.03.044
396.
Losi P, et al. Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice. Acta Biomaterialia. 2013;9:7814-7821.
Not in our library10.1016/j.actbio.2013.04.019
397.
Mo Y, et al. Controlled dual delivery of angiogenin and curcumin by electrospun nanofibers for skin regeneration. Tissue Eng. Part A. 2017;23:597-608.
Not in our library10.1089/ten.tea.2016.0268
398.
Szczesny G, et al. Bacteriology of callus of closed fractures of tibia and femur. J. Trauma. 2008;65:837-842.
Not in our library10.1097/ta.0b013e3181469d44
399.
Framework nucleic acids as programmable carrier for transdermal drug delivery · 2019
No notice
400.
Son J, et al. DNA aptamer immobilized hydroxyapatite for enhancing angiogenesis and bone regeneration. Acta Biomaterialia. 2019;99:469-478.
Not in our library10.1016/j.actbio.2019.08.047
401.
Mao Z, et al. Enhanced angiogenesis of porous collagen scaffolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor. Acta Biomaterialia. 2009;5:2983-2994.
Not in our library10.1016/j.actbio.2009.04.004
402.
Nillesen ST, et al. Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF. Biomaterials. 2007;28:1123-1131.
Not in our library10.1016/j.biomaterials.2006.10.029
403.
Nillesen ST, et al. Increased angiogenesis in acellular scaffolds by combined release of FGF2 and VEGF. J. Control. Release. 2006;116:e88-e90.
Not in our library10.1016/j.jconrel.2006.09.065
404.
Qin X, et al. Tetrahedral framework nucleic acids prevent retina ischemia-reperfusion injury from oxidative stress via activating the Akt/Nrf2 pathway. Nanoscale. 2019;11:20667-20675.
Not in our library10.1039/c9nr07171g
405.
Zhao D, et al. Tetrahedral DNA nanostructure promotes endothelial cell proliferation, migration, and angiogenesis via Notch signaling pathway. ACS Appl. Mater. Interfaces. 2018;10:37911-37918.
Not in our library10.1021/acsami.8b16518
406.
Zhao D, et al. Tetrahedral framework nucleic acid promotes the treatment of bisphosphonate-related osteonecrosis of the jaws by promoting angiogenesis and M2 polarization. ACS Appl. Mater. interfaces. 2020;12:44508-44522.
Not in our library10.1021/acsami.0c13839
407.
Cui W, et al. Preventive effect of tetrahedral framework nucleic acids on bisphosphonate-related osteonecrosis of the jaw. Nanoscale. 2020;12:17196-17202.
Not in our library10.1039/d0nr03731a
408.
Willem de Vries J, et al. DNA nanoparticles for ophthalmic drug delivery. Biomaterials. 2018;157:98-106.
Not in our library10.1016/j.biomaterials.2017.11.046
409.
Rodier JT, et al. Linear polyethylenimine-DNA nanoconstruct for corneal gene delivery. J. Ocul. Pharmacol. Ther. 2019;35:23-31.
Not in our library10.1089/jop.2018.0024
410.
Trigueros S, Domenech EB, Toulis V, Marfany G. In vitro gene delivery in retinal pigment epithelium cells by plasmid dna-wrapped gold nanoparticles. Genes. 2019;10:289.
Not in our library10.3390/genes10040289
411.
Gao S, et al. Tetrahedral framework nucleic acids induce immune tolerance and prevent the onset of type 1 diabetes. Nano Lett. 2021;21:4437-4446.
Not in our library10.1021/acs.nanolett.1c01131
412.
Xia K, et al. Systematic study in mammalian cells showing no adverse response to tetrahedral DNA nanostructure. ACS Appl. Mater. Interfaces. 2018;10:15442-15448.
Not in our library10.1021/acsami.8b02626
413.
Pei H, Zuo X, Zhu D, Huang Q, Fan C. Functional DNA nanostructures for theranostic applications. Acc. Chem. Res. 2014;47:550-559.
Not in our library10.1021/ar400195t
414.
Liang L, et al. Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. Angew. Chem. Int. Ed. Engl. 2014;53:7745-7750.
Not in our library10.1002/anie.201403236
415.
Yang D, Tan Z, Mi Y, Wei B. DNA nanostructures constructed with multi-stranded motifs. Nucleic Acids Res. 2017;45:3606-3611.
Not in our library10.1093/nar/gkx121
416.
Bagalkot V, Farokhzad OC, Langer R, Jon S. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew. Chem. Int. Ed. Engl. 2006;45:8149-8152.
Not in our library10.1002/anie.200602251
417.
Erben CM, Goodman RP, Turberfield AJ. Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Ed. 2006;45:7414-7417.
Not in our library10.1002/anie.200603392
418.
Chou LY, Zagorovsky K, Chan WC. DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination. Nat. Nanotechnol. 2014;9:148-155.
Not in our library10.1038/nnano.2013.309
419.
He Y, et al. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature. 2008;452:198-201.
Not in our library10.1038/nature06597
420.
Iinuma R, et al. Polyhedra self-assembled from DNA tripods and characterized with 3D DNA-paint. Science. 2014;344:65-69.
Not in our library10.1126/science.1250944
421.
Peng R, et al. Facile assembly/disassembly of DNA nanostructures anchored on cell-mimicking giant vesicles. J. Am. Chem. Soc. 2017;139:12410-12413.
Not in our library10.1021/jacs.7b07485
422.
Liu X, Yan H, Liu Y, Chang Y. Targeted cell-cell interactions by DNA nanoscaffold-templated multivalent bispecific aptamers. Small. 2011;7:1673-1682.
Not in our library10.1002/smll.201002292
423.
Shi P, et al. In situ synthesis of an aptamer-based polyvalent antibody mimic on the cell surface for enhanced interactions between immune and cancer cells. Angew. Chem. Int. Ed. Engl. 2020;59:11892-11897.
Not in our library10.1002/anie.202004206
424.
Yong-Xing Z, et al. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano. 2012;6:8684-8691.
Not in our library10.1021/nn3022662
425.
Qian Z, et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano. 2014;8:6633-6643.
Not in our library10.1021/nn502058j
426.
Zhang G, Zhang Z, Yang. J. DNA tetrahedron delivery enhances doxorubicin-induced apoptosis of HT-29 colon cancer cells. Nanoscale Res. Lett. 2017;12:495.
Not in our library10.1186/s11671-017-2272-9
427.
Li S, et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 2018;36:258-264.
Not in our library10.1038/nbt.4071
428.
Vindigni G, et al. Receptor-mediated entry of pristine octahedral DNA nanocages in mammalian cells. ACS Nano. 2016;10:5971-5979.
Not in our library10.1021/acsnano.6b01402
429.
Chang M, Yang C-S, Huang. D-M. Aptamer-conjugated DNA icosahedral nanoparticles as a carrier of doxorubicin for cancer therapy. ACS Nano. 2011;5:6156-6163.
Not in our library10.1021/nn200693a
430.
Taghdisi SM, et al. Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo. Eur. J. Pharm. Biopharm. 2016;102:152-158.
Not in our library10.1016/j.ejpb.2016.03.013
431.
Lee H, et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 2012;7:389-393.
Not in our library10.1038/nnano.2012.73
432.
Liu X, et al. A DNA nanostructure platform for directed assembly of synthetic vaccines. Nano Lett. 2012;12:4254-4259.
Not in our library10.1021/nl301877k
433.
Yang J, et al. Self-assembled double-bundle DNA tetrahedron for efficient antisense delivery. ACS Appl Mater. Interfaces. 2018;10:23693-23699.
Not in our library10.1021/acsami.8b07889
434.
Kim K-R, et al. Sentinel lymph node imaging by a fluorescently labeled DNA tetrahedron. Biomaterials. 2013;34:5226-5235.
Not in our library10.1016/j.biomaterials.2013.03.074
435.
Goodman RP, Berry RM, Turberfield AJ. The single-step synthesis of a DNA tetrahedron. Chem. Commun. (Camb). 2004;21:1372-1373.
Not in our library10.1039/b402293a
436.
Li Z, et al. A replicable tetrahedral nanostructure self-assembled from a single DNA strand. J. Am. Chem. Soc. 2009;131:13093-13098.
Not in our library10.1021/ja903768f
437.
Zhang Y, et al. DNA-affibody nanoparticles for inhibiting breast cancer cells overexpressing HER2. Chem. Commun. (Camb.). 2017;53:573-576.
Not in our library10.1039/c6cc08495h
438.
Sun P, et al. SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer. Int. J. Nanomed. 2017;12:2657-2672.
Not in our library10.2147/ijn.s132929
439.
Ma W, et al. An intelligent DNA nanorobot with in vitro enhanced protein lysosomal degradation of HER2. Nano Lett. 2019;19:4505-4517.
Not in our library10.1021/acs.nanolett.9b01320
440.
Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017;389:2415-2429.
Not in our library10.1016/s0140-6736(16)32417-5
441.
Hyojin Lee D, et al. Enhanced human epidermal growth factor receptor 2 degradation in breast cancer cells by lysosome-targeting gold nanoconstructs. ACS Nano. 2015;9:9859-9867.
Not in our library10.1021/acsnano.5b05138
442.
Mahlknecht G, et al. Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth. Proc. Natl Acad. Sci. USA. 2013;110:8170-8175.
Not in our library10.1073/pnas.1302594110
443.
Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol. 2009;86:151-164.
Not in our library10.1016/j.yexmp.2009.01.004
444.
Reyes-Reyes EM, Salipur FR, Shams M, Forsthoefel MK, Bates PJ. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation. Mol. Oncol. 2015;9:1392-1405.
Not in our library10.1016/j.molonc.2015.03.012
445.
Charoenphol P, Bermudez H. Aptamer-targeted DNA nanostructures for therapeutic delivery. Mol. Pharm. 2014;11:1721-1725.
Not in our library10.1021/mp500047b
446.
Xia Z, et al. Tumor-penetrating peptide-modified DNA tetrahedron for targeting drug delivery. Biochemistry. 2016;55:1326-1331.
Not in our library10.1021/acs.biochem.5b01181
447.
Setyawati MI, Kutty RV, Leong DT. DNA nanostructures carrying stoichiometrically definable antibodies. Small. 2016;12:5601-5611.
Not in our library10.1002/smll.201601669
448.
Miao P, Wang B, Chen X, Li X, Tang Y. Tetrahedral DNA nanostructure-based microRNA biosensor coupled with catalytic recycling of the analyte. ACS Appl Mater. Interfaces. 2015;7:6238-6243.
Not in our library10.1021/acsami.5b01508
449.
Liu X, Wu L, Wang L, Jiang W. A dual-targeting DNA tetrahedron nanocarrier for breast cancer cell imaging and drug delivery. Talanta. 2018;179:356-363.
Not in our library10.1016/j.talanta.2017.11.034
450.
Fu W, et al. Enhanced efficacy of temozolomide loaded by a tetrahedral framework DNA nanoparticle in the therapy for glioblastoma. ACS Appl Mater. Interfaces. 2019;11:39525-39533.
Not in our library10.1021/acsami.9b13829
451.
Chen CH, et al. Aptamer-based endocytosis of a lysosomal enzyme. Proc. Natl Acad. Sci. USA. 2008;105:15908-15913.
Not in our library10.1073/pnas.0808360105
452.
Tian Y, Huang Y, Gao P, Chen T. Nucleus-targeted DNA tetrahedron as a nanocarrier of metal complexes for enhanced glioma therapy. Chem. Commun. (Camb.). 2018;54:9394-9397.
Not in our library10.1039/c8cc04021d
453.
Bugaj AM. Targeted photodynamic therapy–a promising strategy of tumor treatment. Photochem Photobio. Sci. 2011;10:1097-1109.
Not in our library10.1039/c0pp00147c
454.
Kim K-R, Bangb D, Ahn. D-R. Nano-formulation of a photosensitizer using a DNA tetrahedron and its potential for in vivo photodynamic therapy. Biomater. Sci. 2016;4:605-609.
Not in our library10.1039/c5bm00467e
455.
Zhuang X, et al. A photosensitizer-loaded DNA origami nanosystem for photodynamic therapy. ACS Nano. 2016;10:3486-3495.
Not in our library10.1021/acsnano.5b07671
456.
Bujold KE, Hsu JCC, Sleiman HF. Optimized DNA “nanosuitcases” for encapsulation and conditional release of siRNA. J. Am. Chem. Soc. 2016;138:14030-14038.
Not in our library10.1021/jacs.6b08369
457.
A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery · 2016
No notice
458.
Zhang Q, et al. Anti-inflammatory and antioxidative effects of tetrahedral dna nanostructures via the modulation of macrophage responses. ACS Appl. Mater. interfaces. 2018;10:3421-3430.
Not in our library10.1021/acsami.7b17928
459.
Zhang Y, et al. Inhibiting methicillin-resistant Staphylococcus aureus by tetrahedral DNA nanostructure-enabled antisense peptide nucleic acid delivery. Nano Lett. 2018;18:5652-5659.
Not in our library10.1021/acs.nanolett.8b02166
460.
Zhang Y, et al. Multi-targeted antisense oligonucleotide delivery by a framework nucleic acid for inhibiting biofilm formation and virulence. Nano-Micro Lett. 2020;12:74.
Not in our library10.1007/s40820-020-0409-3
461.
Gerling T, Wagenbauer KF, Neuner AM, Dietz H. Dynamic DNA devices and assemblies formed by shape-complementary, non-base pairing 3D components. Science. 2015;347:1446-1452.
Not in our library10.1126/science.aaa5372
462.
Wu C, et al. Building a multifunctional aptamer-based DNA nanoassembly for targeted cancer therapy. J. Am. Chem. Soc. 2013;135:18644-18650.
Not in our library10.1021/ja4094617
463.
Zhu G, et al. Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. Proc. Natl Acad. Sci. USA. 2013;110:7998-8003.
Not in our library10.1073/pnas.1220817110
464.
Lv Y, et al. Preparation and biomedical applications of programmable and multifunctional DNA nanoflowers. Nat. Protoc. 2015;10:1508-1524.
Not in our library10.1038/nprot.2015.078
465.
Da H, et al. Engineering a cell-surface aptamer circuit for targeted and amplified photodynamic cancer therapy. ACS Nano. 2013;7:2312-2319.
Not in our library10.1021/nn305484p
466.
Li W, et al. Self-assembled DNA nanocentipede as multivalent drug carrier for targeted delivery. ACS Appl. Mater. Interfaces. 2016;8:25733-25740.
Not in our library10.1021/acsami.6b08210
467.
Zadegan RM, et al. Construction of a 4 zeptoliters switchable 3D DNA box origami. ACS Nano. 2012;6:10050-10053.
Not in our library10.1021/nn303767b
468.
Douglas SM, Bachelet I, Church. GM. A logic-gated nanorobot for targeted transport of molecular payloads. Science. 2012;335:831-834.
Not in our library10.1126/science.1214081
469.
Wang Y, Jiang LP, Zhou S, Bi S, Zhu JJ. DNA polymerase-directed hairpin assembly for targeted drug delivery and amplified biosensing. ACS Appl Mater. Interfaces. 2016;8:26532-26540.
Not in our library10.1021/acsami.6b08597
470.
Bi S, Xiu B, Ye J, Dong Y. Target-catalyzed DNA four-way junctions for cret imaging of microrna, concatenated logic operations, and self-assembly of DNA nanohydrogels for targeted drug delivery. ACS Appl Mater. Interfaces. 2015;7:23310-23319.
Not in our library10.1021/acsami.5b07827
471.
Li J, et al. Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive property for targeted gene regulation therapy. J. Am. Chem. Soc. 2015;137:1412-1415.
Not in our library10.1021/ja512293f
472.
Daljit Singh JK, Luu MT, Abbas A, Wickham SFJ. Switchable DNA-origami nanostructures that respond to their environment and their applications. Biophys. Rev. 2018;10:1283-1293.
Not in our library10.1007/s12551-018-0462-z
473.
Endo M, Sugiyama H. DNA origami nanomachines. Molecules. 2018;23:1766.
Not in our library10.3390/molecules23071766
474.
Kuzuya A, Sakai Y, Yamazaki T, Xu Y, Komiyama M. Nanomechanical DNA origami ‘single-molecule beacons’ directly imaged by atomic force microscopy. Nat. Commun. 2011;2:449.
Not in our library10.1038/ncomms1452
475.
Bernard Y, et al. A DNA-fuelled molecular machine made of DNA. nature. 2000;406:605-608.
Not in our library10.1038/35020524
476.
Kuzuya A, et al. Nanomechanical DNA Origami pH. Sens. Sens. 2014;14:19329-19335.
Not in our library10.3390/s141019329
477.
Zadegan RM, Jepsen MD, Hildebrandt LL, Birkedal V, Kjems J. Construction of a fuzzy and Boolean logic gates based on DNA. Small. 2015;11:1811-1817.
Not in our library10.1002/smll.201402755
478.
Amir Y, et al. Universal computing by DNA origami robots in a living animal. Nat. Nanotechnol. 2014;9:353-357.
Not in our library10.1038/nnano.2014.58
479.
Bao-an C, et al. Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and MDr1 shrNA expression vector in leukemia cells. Int. J. Nanomed. 2010;5:437-444.
Not in our library10.2147/ijn.s10083
480.
Mariagrazia M, et al. P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia. Br. J. Haematol. 2000;108:703-709.
Not in our library10.1046/j.1365-2141.2000.01957.x
481.
Morris SA, Farrell D, Grodzinski P. Nanotechnologies in cancer treatment and diagnosis. J. Natl Compr. Cancer Netw. 2014;12:1727-1733.
Not in our library10.6004/jnccn.2014.0175
482.
Qiao J, et al. DNA origami as a carrier for circumvention of drug resistance. J. Am. Chem. Soc. 2012;134:13396-13403.
Not in our library10.1021/ja3003183
483.
Liu J, et al. Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance. Biomaterials. 2016;91:44-56.
Not in our library10.1016/j.biomaterials.2016.03.013
484.
Mei L, et al. Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery. Nano Res. 2015;8:3447-3460.
Not in our library10.1007/s12274-015-0841-8
485.
Fu J, et al. DNA-scaffolded proximity assembly and confinement of multienzyme reactions. Top. Curr. Chem. (Cham). 2020;378:38.
Not in our library10.1007/s41061-020-0299-3
486.
Hiroaki H, et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740-745.
Not in our library10.1038/35047123
487.
Arthur MK, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 1995;374:546-549.
Not in our library10.1038/374546a0
488.
Gupta GK, Agrawal DK. CpG oligodeoxynucleotides as TLR9 agonists therapeutic application in allergy and asthma. Biodrugs. 2010;24:225-235.
Not in our library10.2165/11536140-000000000-00000
489.
Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv. Drug Deliv. Rev. 2009;61:195-204.
Not in our library10.1016/j.addr.2008.12.008
490.
Schu ¨ ller VJ, et al. Cellular immunostimulation by CpG-sequence-coated DNA origami structures. ACS Nano. 2011;5:9696-9702.
Not in our library10.1021/nn203161y
491.
Sellner S, et al. DNA nanotubes as intracellular delivery vehicles in vivo. Biomaterials. 2015;53:453-463.
Not in our library10.1016/j.biomaterials.2015.02.099
492.
Rattanakiat S, Nishikawa M, Funabashi H, Luo D, Takakura Y. The assembly of a short linear natural cytosine-phosphate-guanine DNA into dendritic structures and its effect on immunostimulatory activity. Biomaterials. 2009;30:5701-5706.
Not in our library10.1016/j.biomaterials.2009.06.053
493.
Mohri K, et al. Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA to immune cells. Biomacromolecules. 2015;16:1095-1101.
Not in our library10.1021/bm501731f
494.
Jiang LI, et al. Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano. 2011;5:8783-8789.
Not in our library10.1021/nn202774x
495.
Ouyang X, et al. Rolling circle amplification-based DNA origami nanostructrures for intracellular delivery of immunostimulatory drugs. Small. 2013;9:3082-3087.
Not in our library10.1002/smll.201300458
496.
de Vries JW, Zhang F, Herrmann A. Drug delivery systems based on nucleic acid nanostructures. J. Control Release. 2013;172:467-483.
Not in our library10.1016/j.jconrel.2013.05.022
497.
Nishikawa M, Matono M, Rattanakiat S, Matsuoka N, Takakura Y. Enhanced immunostimulatory activity of oligodeoxynucleotides by Y-shape formation. Immunology. 2008;124:247-255.
Not in our library10.1111/j.1365-2567.2007.02762.x
498.
Kohta M, et al. Design and development of nanosized DNA assemblies in polypod-like structures as efficient vehicles for immunostimulatory CpG motifs to immune cells. ACS Nano. 2012;6:5931-5940.
Not in our library10.1021/nn300727j
499.
Hu J, Liu MH, Zhang CY. Construction of tetrahedral DNA-quantum dot nanostructure with the integration of multistep forster resonance energy transfer for multiplex enzymes assay. ACS Nano. 2019;13:7191-7201.
Not in our library10.1021/acsnano.9b02679
500.
Ma F, Zhang Q, Zhang CY. Catalytic self-assembly of quantum-dot-based MicroRNA nanosensor directed by toehold-mediated strand displacement cascade. Nano Lett. 2019;19:6370-6376.
Not in our library10.1021/acs.nanolett.9b02544
501.
Aptamer Display on Diverse DNA Polyhedron Supports · 2018
Not checked
502.
Tian T, et al. Targeted imaging of brain tumors with a framework nucleic acid probe. ACS Appl. Mater. Interfaces. 2018;10:3414-3420.
Not in our library10.1021/acsami.7b17927
503.
Zhang K, et al. DNA tetrahedron based biosensor for argonaute2 assay in single cells and human immunodeficiency virus type-1 related ribonuclease H detection in vitro. Anal. Chem. 2019;91:7086-7096.
Not in our library10.1021/acs.analchem.9b00011
504.
Li N, et al. A DNA tetrahedron nanoprobe with controlled distance of dyes for multiple detection in living cells and in vivo. Anal. Chem. 2017;89:6670-6677.
Not in our library10.1021/acs.analchem.7b00889
505.
Li C, et al. Design of DNA nanostructure-based interfacial probes for the electrochemical detection of nucleic acids directly in whole blood. Chem. Sci. 2018;9:979-984.
Not in our library10.1039/c7sc04663d
506.
Jiang D, et al. Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl Mater. Interfaces. 2016;8:4378-4384.
Not in our library10.1021/acsami.5b10792
507.
Feng QM, Zhu MJ, Zhang TT, Xu JJ, Chen HY. A novel DNA tetrahedron-hairpin probe for in situ“off-on” fluorescence imaging of intracellular telomerase activity. Analyst. 2016;141:2474-2480.
Not in our library10.1039/c6an00241b
508.
Bi X, Yin J, Chen Guanbang A, Liu CF. Chemical and enzymatic strategies for bacterial and mammalian cell surface engineering. Chemistry (Easton). 2018;24:8042-8050.
Not in our library10.1002/chem.201705049
509.
Aghebat Rafat A, Sagredo S, Thalhammer M, Simmel FC. Barcoded DNA origami structures for multiplexed optimization and enrichment of DNA-based protein-binding cavities. Nat. Chem. 2020;12:852-859.
Not in our library10.1038/s41557-020-0504-6
510.
Gartner ZJ, Bertozzi CR. Programmed assembly of 3-dimensional microtissues with defined cellular connectivity. Proc. Natl Acad. Sci. USA. 2009;106:4606-4610.
Not in our library10.1073/pnas.0900717106
511.
Akbari, E. et al. Engineering cell surface function with DNA origami. Adv. Mater.29, 10.1002/adma.201703632(2017).
Not in our library10.1002/adma.201703632
512.
Sacca B, et al. Orthogonal protein decoration of DNA origami. Angew. Chem. Int. Ed. Engl. 2010;49:9378-9383.
Not in our library10.1002/anie.201005931
513.
Li H, Han M, Weng X, Zhang Y, Li J. DNA-tetrahedral-nanostructure-based entropy-driven amplifier for high-performance photoelectrochemical biosensing. ACS Nano. 2021;15:1710-1717.
Not in our library10.1021/acsnano.0c09374
514.
Kizer ME, Linhardt RJ, Chandrasekaran AR, Wang X. A Molecular hero suit for in vitro and in vivo dna nanostructures. Small. 2019;15:e1805386.
Not in our library10.1002/smll.201805386
515.
Tian T, et al. Proteomic exploration of endocytosis of framework nucleic acids. Small. 2021;17:e2100837.
Not in our library10.1002/smll.202100837
516.
Li J, Fan C, Pei H, Shi J, Huang Q. Smart drug delivery nanocarriers with self-assembled DNA nanostructures. Adv. Mater. 2013;25:4386-4396.
Not in our library10.1002/adma.201300875
517.
Walsh AS, Yin H, Erben CM, Wood MJ, Turberfield AJ. DNA cage delivery to mammalian cells. ACS Nano. 2011;5:5427-5432.
Not in our library10.1021/nn2005574
518.
Yuan Y, Gu Z, Yao C, Luo D, Yang D. Nucleic acid-based functional nanomaterials as advanced cancer therapeutics. Small. 2019;15:e1900172.
Not in our library10.1002/smll.201900172
519.
Sun Y, et al. Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli). Bioact. Mater. 2021;6:2281-2290.
Not in our library10.1016/j.bioactmat.2020.12.027
520.
Multi-functional DNA nanostructures that puncture and remodel lipid membranes into hybrid materials · 2018
Not checked
521.
Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles · 2021
No notice
522.
Bhalla N, Pan Y, Yang Z, Payam AF. Opportunities and challenges for biosensors and nanoscale analytical tools for pandemics: COVID-19. ACS Nano. 2020;14:7783-7807.
Not in our library10.1021/acsnano.0c04421
523.
Shen Q, Grome MW, Yang Y, Lin C. Engineering lipid membranes with programmable DNA nanostructures. Adv. Biosyst. 2020;4:1900215.
Not in our library10.1002/adbi.201900215
524.
Ji X, et al. Epigenetic remodeling hydrogel patches for multidrug-resistant triple-negative breast cancer. Adv. Mater. 2021;33:e2100949.
Not in our library10.1002/adma.202100949
525.
Zhou Y, et al. An organelle-specific nanozyme for diabetes care in genetically or diet-induced models. Adv. Mater. 2020;32:e2003708.
Not in our library10.1002/adma.202003708
526.
Han J, Cui Y, Li F, Gu Z, Yang D. Responsive disassembly of nucleic acid nanocomplex in cells for precision medicine. Nano Today. 2021;39:101160.
Not in our library10.1016/j.nantod.2021.101160

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