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Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity

Laís Salomão Arias, Juliano Pelim Pessan, Ana Paula Miranda Vieira and 3 more

Antibiotics · 2018 · Review · CC BY

doi:10.3390/antibiotics7020046

Abstract

Medical applications and biotechnological advances, including magnetic resonance imaging, cell separation and detection, tissue repair, magnetic hyperthermia and drug delivery, have strongly benefited from employing iron oxide nanoparticles (IONPs) due to their remarkable properties, such as superparamagnetism, size and possibility of receiving a biocompatible coating. Ongoing research efforts focus on reducing drug concentration, toxicity, and other side effects, while increasing efficacy of IONPs-based treatments. This review highlights the methods of synthesis and presents the most recent reports in the literature regarding advances in drug delivery using IONPs-based systems, as well as their antimicrobial activity against different microorganisms. Furthermore, the toxicity of IONPs alone and constituting nanosystems is also addressed.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 17, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

The development of nanotechnology has provided resources to various applications in the medical field, leading to significant advances in terms of diagnosis, biological detection, therapy and drug delivery. In this context, magnetic nanoparticles comprise important characteristics that make them attractive for a variety of biomedical applications, including contrast agents in magnetic resonance imagining (MRI), cell separation and detection, treatment for hyperthermia and drug delivery. Specifically, iron oxide magnetic nanoparticles (IONPs) are physically and chemically stable, biocompatible and environmentally safe, thus presenting unique characteristics for clinical applications. However, when IONPs (Fe3O4 (magnetite) or γ-Fe2O3 (maghemite)) reach smaller sizes (about 10–20 nm for iron oxide), superparamagnetic properties become evident, so that the particles reach a better performance for most of the aforementioned applications.

Despite the growing body of evidence attesting their biomedical usefulness, superparamagnetic IONPs are still in early stage of clinical investigation, with studies pointing out to the need for their improvement prior to their commercialization. Most of clinical trials with IONPs have been developed within the last decade, being MRI imaging the main application assessed. The number of clinical trials indexed on clinicaltrials.gov under the term ‘iron oxide nanoparticles’ comprises fourteen protocols. Of these, four are completed, four are still active, one was withdrawn, four were suspended or terminated, and one has an unknown status. Published data from one of those clinical trials showed that IONPs succeeded to act as contrast agent for MRI for the assessment of cellular myocardial inflammation following acute myocardial infarction, with no described adverse effects to the patients.

Issues related to biocompatibility, toxicological and immunological parameters are other challenges that need to be addressed. Data on methods of synthesis show that IONPs functions are directly related to size, shape, coating and stability of these nanoparticles. As an example, large nanoparticles (>200 nm) are easily cleared by the reticuloendothelial system, while particles smaller than 10 nm are easily excreted from the body through existent pores of the kidney’s basal lamina, what reduces their blood-circulating time. Further, hydrophobic and negatively charged nanoparticles tend to suffer proteic opsonization and are quickly recognized by phagocytic cells, also resulting in faster clearance. These and other IONPs limitations, such as oxidation and cell toxicity, can be overcome by an adequate surface-coating, implying that the success of a IONPs-based nanosystem is also directly related to the properties of the coating material. Different organic and inorganic coatings, including natural and synthetic polymers, surfactants, gold, silica and peptides have been investigated in studies showing that shape, spatial configuration and nature of the coating play an important role on the nanosystem’s performance.

This review provides conceptual information on methods of IONPs synthesis, addressing the main advantages and disadvantages, and drugs bound to IONPs in the production of drug-delivery nanosystems. The latest updates on bioapplications, translational advances, and the employment of IONPs on antimicrobial therapeutic alternatives are also covered, bringing new perspectives on IONPs investigations. Finally, a set of considerations is made on IONPs toxicological aspects, as well as advances on coating strategies to elaborate more biocompatible nanosystems.

2. Synthesis of IONPs

There are three main routes for the synthesis of IONPs: chemical, physical and biological. These have been investigated in order to produce more stable, soluble, biocompatible, and shape and size-controlled nanoparticles. This review presents an overview on the most common methods of synthesis, highlighting advantages and disadvantages of each method.

2.1.1. Co-Precipitation

Among the chemical methods of synthesis of IONPs, the aqueous co-precipitation is the most commonly used. Shortly, salts of Fe2+ and Fe3+ ions suffer co-precipitation in a fairly basic solution (molar ratio 1:2) at room temperature or under heat. In general, this is a convenient and low cost method that enables rapid large-scale production. However, the resulting nanoparticles present problems of aggregation and large size distribution, which is common in aqueous routes, in addition to poor crystallinity and tendency to oxidize, thus compromising their magnetic properties.

Given that base concentration, temperature, Fe2+/Fe3+ proportion, value and ionic strength of the media, order of the reactants and the use of surfactants are factors that may interfere with the control of particle size, shape, composition and magnetic properties, recent studies have adapted the co-precipitation method in order to improve the properties of the nanoparticles. For instance, through variations in the pH of the precipitates and in the amount of sodium hydroxide, spherical IONPs of different sizes can be obtained, taking advantage of the linear relation between IONPs diameter and pH, probably due to nanoparticle aggregation.

2.1.2. Microemulsion

The microemulsion method acts confining the production of nanoparticles inside a nanosystem that combines a stable isotropic mixture of oil and water, whose interface is stabilized by a monolayer of surfactant, sometimes combined with a co-surfactant. The size of the microemulsion, whether direct (oil dispersed in water) or indirect (water dispersed in oil), may be controlled by adjusting the ratio of water, oil and surfactant, which consequently leads to the IONPs size control. Microemulsion experiments demonstrated that the nature of the surfactant, concentration of Fe2+/Fe3+ ions, as well as the temperature and the pH value strongly influence the nanoparticles size distribution and, consequently, their magnetization. Despite the narrow size distribution that this method provides, it presents certain limitations for biomedical purposes, including requirements of low temperatures and large quantity of oil, which limits large scale production. Moreover, surfactants adhered to IONPs are difficult to remove.

2.1.3. Hydrothermal and Solvothermal Syntheses

Through the hydrothermal method, iron precursors are exposed to vapor in a sealed container, under high pressure and temperature conditions in an aqueous medium, creating uniform IONPs. Under these conditions, the controlled oxidation of Fe3O4 and the mineralization of Fe3+ ions occur. When the aqueous synthesis methods generate particles with low crystallization, the solvothermal method can be used, which consists in replacing water by other organic solvents, allowing the formation of monodisperse IONPs with high crystallinity and controlled shape. However, such methods last much longer (hours to days) in comparison to the microemulsion method.

2.1.4. Thermal Decomposition

The thermal decomposition is a non-aqueous synthesis in which organometallic compounds such as Fe(Acac)3, Fe(C2O4) × 2H2O, Fe(CH3COO)2 or ferrocene suffer decomposition in a high-boiling organic solvent (or via solvent free) in the presence of stabilizing surfactants like aliphatic amine and fatty acids. This method circumvents the limitations of co-precipitation by generating high quality IONPs with close distribution and particle size control, as well as improving their magnetism and degree of crystallinity. This occurs due to the possibility of separating the nucleation from the growth, avoiding complex reactions of hydrolysis. Iron oxide nanocrystals with narrow size distributions, high yield and without aggregation can be obtained by this method. However, as the resulting IONPs are insoluble in water, further steps are required to make their surfaces hydrophilic and, consequently, compatible with biological solutions. Also, a higher relaxivity and saturation magnetization can be achieved by higher temperatures and shorter synthesis reactions.

2.1.5. Sol-Gel Reaction and Polyol

The sol-gel reaction is a wet-chemical method in which iron alkoxides and salts (e.g., chlorides, nitrates and acetates) undergo reactions of condensation and hydrolysis. Factors implicated in the process such as pH, temperature and concentration of the reagents can interfere with the final crystallinity of the product. The main advantage of this method is the production of structures with good homogeneity and size, and high purity and quantity. However, precursors used in the reaction are costly, and the resulting nanoparticles may display high permeability and low wear resistance. On the other hand, the polyol method uses a reduction reaction in which the polyol is heated to its boiling point, and acts as a solvent and reducing agent in a medium with iron precursors, controlling the growth of the particles. Noteworthy, the size of the nanoparticles varies according with the polyol used, reaction time and concentration of iron precursor. In this sense, the size of the nanoparticles was shown to increase proportionally to the length of the glycol.

2.1.6. Sonochemical

In sonochemical synthesis, a ferrous salt solution is subjected to a high-intensity ultrasonication at room temperature, ensuring that the physical effects generated from the creation of blistering in solution generates the energy required for the reaction. This method can be an unusual and versatile alternative for materials synthesis owing to short reaction times, and lack of high process temperature and pressure. As an example, the highest percentage of atomic concentration when functionalizing 3-amino propyl triethoxyl silane with IONPs was achieved after one minute of sonication. In addition, the ultrasonic frequency may play a role in the products generated by this method, considering that the amount of the drug loaded proportionally increases with ultrasound frequency.

2.1.7. Microwave-Assisted Synthesis

Microwave-assisted synthesis is a relatively simple and recent method, in which a mixture containing the iron precursors is exposed to microwave electromagnetic radiation, causing molecule reorientation, and strong and homogeneous internal heating. This method has several advantages such as low-cost, reduced time of reaction and narrow size- and shape-control of the IONPs, which make it attractive for cost-efficient commercial production of IONPs with appropriate solubility and biocompatibility for clinical trials.

2.2.1. Pyrolysis Method

In pyrolysis method, gaseous (aerosol) organometallic precursors are exposed to laser radiation that transmits energy in a selective way, according to the chemicals wavelength, thus generating IONPs. This route produces pure and homogeneous samples with good size control and shape distribution. It is less expensive than other methods, since it operates at atmospheric pressure. Factors such as precursors concentration, working pressure and laser intensity directly interfere with size and magnetization of the resulting nanoparticles.

2.2.2. Laser Ablation Synthesis in Solution (LASiS)

This synthesis is triggered when a pulsed laser beam reaches the target material immersed in liquid solution, causing changes in the composition of the ablation target and in the liquid solution. Although LASiS is an interesting technique for materials of different structures and compositions, this method carries problems depending on the solvent used, such as the difficulty of controlling particle size and their clustering. Recent experiments, however, revealed that the use of laser ablation on phosphonates aqueous solution and bulk iron was successful in decreasing the size of FeOx crystal to few atom clusters.

Biosynthesis

Biosynthesis stands out as a simple, low-cost and eco-friendly route of IONPs production, in which plant extracts or microbial-derived products with reducing potential interact with iron precursors under stirring. The main reaction involved in this process is reduction/oxidation, and the resulting nanoparticles usually display good biocompatibility. The IONPs biosynthesis can use iron-reducing bacteria such as Geobacter metallireducens but may include many other possibilities. One example is the synthesis by the enzyme lumazine synthase (produced both by fungi and bacteria), which serves as a biological nanoreactor, synthesizing IONPs inside narrow-diameter capsid templates.

3. IONPs Coating and Functionalization

Core-shell nanosystems are often employed to attach different drugs to IONPs. The nanoparticle corresponds to the core, while shell represents the surface coating for nanoparticle functionalization, improving its stability, pharmacokinetics, biodistribution and biocompatibility. Synthetic and natural polymers, organic surfactants, inorganic compounds and bioactive molecules can function as shell of IONPs, as summarized in Figure 1.

3.1. Synthetic and Natural Polymers

Polymers are the most common surface coating used in IONPs, since they can prevent oxidation and confer stability to the nanoparticles. The polymer nature can be synthetic, encompassing polyethylene glycol, poly(vinylpyrrolidone), polyvinyl alcohol and poly(lactic-co-glycolic acid), or natural, as in the case of chitosan.

3.1.1. Polyethylene Glycol (PEG)

PEG is a hydrophilic, uncharged polyether polymer well known for its biocompatibility. It has been commonly used as IONPs-coating due to non-fouling properties, reduced blood proteins opsonization and, as a result, escapes recognition by the immune system. Such properties increase its time in blood circulation and the accumulation in the target cells/organ.

3.1.2. Poly(vinylpyrrolidone) (PVP) e Polyvinyl Alcohool (PVA)

PVP e PVA are water-soluble synthetic polymers. Specifically, PVP is derived from the monomer N-vinyl pyrrolidone. Given its biocompatible, stable and safe properties, PVP is widely used in biomedical and pharmaceutical applications. In turn, PVA exhibits emulsifying and adhesive properties, forming a hydrogel structure that involves the IONPs by means of hydrogen bonds between the polymer chains. This leads to increases in polymer-surface interactions, preventing the agglomeration of the particles.

3.1.3. Poly(lactic-co-glycolic acid) (PLGA)

PLGA is a copolymer of poly lactic acid and poly glycolic acid (PGA) with great potential for use in drug delivery and tissue engineering. Besides presenting solubility in most of common solvents, PLGA can take different shapes and sizes, and encapsulates molecules of all sizes. Usually, higher rates of PGA (which contains methyl site groups) lead to a higher hydrophobicity and degradation of the polymer. On the other hand, lactide-rich PLGA are less hydrophilic and degrade more slowly, since it absorbs less water. Moreover, physical properties of PLGA are known to vary depending on different factors such as the molecular weight, which plays an important role in the drug-loading capacity on the polymer surface.

3.1.4. Chitosan (CS)

IONPs have also been coated with CS. This material is a natural, long-chain polymer, generated by the combination of 2-amino-2-deoxy-β-d-glucan with glycosidic linkages, which can be obtained by chitin deacetylation. Its positive charge drives the CS carriers to the cell membrane (negatively charged) and its mucoadhesive properties extend the CS retention in the target sites, making it interesting for application in drug delivery systems. Furthermore, CS is biocompatible, biodegradable and presents low toxicity.

Many CS-nanosystems have been developed over the last few years, relying on the aforementioned advantages and water solubility. Coating of IONPs with this polymer does not change the thermal and magnetic properties of the nanoparticles, serving as support for drug binding. Also, a one-pot synthesis in the presence of CS of low molecular weight showed that it was capable of protecting IONPs from aggregation due to the electrostatic repulsion between the positively charged nanoparticles.

This polymer, however, presents certain limitations as a coating material, mainly associated with the partial protonation of its amino groups in water at physiological pH, what reduces CS solubility. To overcome such issues, chemical changes can be performed in order to make CS derivatives more water-soluble. A practical example is the O-carboxymethyl CS, which uses hydrogen bonding between water and the polymer in combination with carboxyl group to obtain water solubilization. Also, a polyelectrolyte complex of carboxymethyl starch-CS can be used as a coating for IONPs, producing stable, biocompatible and mucoadhesive nanosystems.

3.2. Organic Surfactants

Surfactants (e.g., oleic acid, lauric acid) are extensively used to functionalize IONPs, mainly when synthesized in organic solutions. IONPs coated with dimercaptosuccinic acid (DMSA) have an anionic surface, which avoids opsonization and clearance by the reticuloendothelial system, with consequent reduction of cell toxicity. Oleic acid and trisodium citrate are also capable of stabilizing nanoparticles by creating repulsive forces (mainly steric repulsion) to balance the magnetic and van der Waals attractive forces.

However, the long hydrocarbon chains of the surfactants make the nanoparticles hydrophobic, hindering their application in vivo, and require measures to prevent or reverse this aspect. Investigations to overcome these limitations led to experiments with surfactant-functionalized IONPs through hydrophobic interactions, demonstrating that lower values of surfactants’ critical micelle concentrations were associated with more efficient coating of the IONPs, with greater dispersion in solutions and lower nanoparticle clustering.

3.3. Inorganic Compounds

Some applications are favored in inorganic compound-containing nanosystems, such as catalysis, bioseparation, optical bioimaging and biological labeling. Moreover, inorganic compounds have the potential to increase the antioxidant properties of bulk IONPs. Silica, carbon, metals, oxides (metal and non-metal) and sulfides are the most widely tested.

SiO2 is a classical coating material for IONPs, since it has the capacity of enhancing the IONPs dispersion in solutions, and to turn them more stable and protected in acidic medium. The silanol groups on their surface also offer perfect anchorage for ligands, providing various functional groups to the nanosystem. Most of silica coatings also contribute to reduce the IONPs toxicity.

Carbon-based coatings have interesting features, such as chemical and thermal stability, good electrical conductivity, solubility, and serve as a barrier against IONPs oxidation, being useful for diverse applications. As an example, novel nanosystem composed by magnetic carbon/Fe3O4 with nanoscale zero-valent iron was able to remove 99.7% of Pb(II) from aqueous solutions.

Metal coatings can also prevent IONPs oxidation owing to their low reactivity. They can bind to IONPs via electrostatic linking, forming core-shell structures that can be modified according to their functional groups and surface charges. In this regard, the electron transfer between silver and IONPs in a nanosystem creates a silver coating positively charged, allowing the conjugation of different antibiotics to the silver-decorated IONPs. In addition, silver coating does not alter the magnetic properties of the original iron oxide powder. Finally, metal coatings can also suffer modifications with compounds such as thiol to enable their linkage with diverse biomolecules.

Oxide and sulfide are common in IONPs functionalization, in order to stabilize the nanosystem without interfering with its magnetic features. For metal oxides, it is possible that the combination of two different magnetic phases creates a new composite with pronounced magnetic properties. The nanosystem can be formed by oxidation of the outer shell of the nanoparticles or it can just be additionally deposited. The choice of a coating for the IONPs must take into account their intrinsic properties and the purpose of the nanosystem. For instance, ZnO was selected as the most appropriate compound for an anticancer nanosystem due to both its intrinsic anticancer properties and biocompatibility.

3.4. Bioactive Molecules

In this category are included bioactive structures such as lipids, peptides, and proteins. In IONPs-based nanosystems functionalized with peptides, the biomolecules are able to maintain the stability of the nanostructures, as well as the magnetic properties of the IONPs.

Human and bovine serum albumin (HSA and BSA) are also used in biomedical and pharmaceutical applications, and can be attached to IONPs by desolvation. BSA-coated IONPs has a negatively charged surface that avoids electrostatic interactions with negative biological elements such as plasma and blood cells, therefore maintaining IONPs stability.

While for matrix-dispersed structures IONPs are distributed in a matrix, thus preventing aggregation, in shell-core-shell they are confined between two functional materials. In turn, Janus particles possess two compartments, one being the IONPs with magnetic properties and the other, composed by different functional molecules.

4. Drugs Bound to IONPs

Magnetic nanoparticles have greater reactive area and ability to cross biological barriers than their micrometric counterparts, which favors their use in drug delivery systems. In this context, different classes of drugs can be directly bound to IONPs or to core-shell nanosystems, as shown in Figure 2. Such binding can occur by adsorption, dispersion in the polymer matrix, encapsulation in the nucleus, electrostatic interactions and covalent attachment to the surface, aiming to improve their pharmacological properties. IONPs have been used as carriers of anticancer, alternative, immunosuppressive, anticonvulsant, anti-inflammatory, antibiotic and antifungal agents.

4.1. Anticancer Drugs

One of the major challenges in cancer treatment is the tolerance developed throughout the therapy, which reduces response to the medicament. When a drug is bound to IONPs, this tolerance can be overcome due to a reduction of the “efflux pumps” that transport the drug to the outside of the cell, what ultimately promotes an increase in drug concentration in cancerous tissues. IONPs-based nanocarriers are also able to reduce undesired interactions with other molecules and toxic effects on normal tissues. Furthermore, these nanosystems are less specific than molecules such as antibodies and peptides, thus acting on various types of cancer.

Over the last two years, the main anticancer drug coupled to IONPs was doxorubicin (DOX). This drug can be covalently bound to functionalized IONPs or establish electrostatic interactions with negatively charged groups present in the magnetic nanocarriers. A nanosystem with mesoporous hydroxyapatite (HA)-coated IONPs for DOX release was able to incorporate 93% of DOX from a concentration of 5 ppm. In 24 h, only 10% of the DOX was released at pH 7.4, while for pH 5.5 it reached a release of 70%, making IONPs-DOX-HA a favorable nanosystem for the treatment of acidic solid tumors.

Current investigations have also synthesized IONPs employing different shells with anticancer agents conventionally administered, such as β-cyclodextrin, carmustine, cetuximab, cytarabine, daunomycin, docetaxel, epirubicin, 5-fluorouracil, gemcitabine, methotrexate, mitoxantrone and paclitaxel. It is noteworthy, however, that these nanosystems demonstrate magnetic properties only in the presence of external magnetic fields to prevent agglomerations of nanoparticles and to allow a satisfactory performance in the target sites.

4.2. Alternative Drugs

Alternative drugs may also be linked to nanosystems. Curcumin, a natural polyphenolic hydrophobic compound from Curcuma longa rhizomes, has been incorporated into IONPs for preventing and fighting cancer. It is believed that this herbal product remains captured at the hydrophobic interface between components of surfactant-stabilized nanocarriers. In this sense, Unterweger et al. proposed the use of photodynamic therapy associated with the hypericin photosensitizer (a component of the plant Hypericum perforatum or St. John’s wort, with antitumor properties), IONPs and dextran, concluding that this combination is a promising alternative for cancer treatment. Hypericin was covalently coupled to dextran-coated IONPs by glutaraldehyde, and the particles of this nanosystem were able to induce the death of cancer cells, besides not presenting agglomeration even after 12 weeks of storage in water.

Another active component of herbal origin used to fight cancer cells is berberine, which exhibits poor bioavailability in tumor sites due to the lack of hydrophilicity. To address this limitation, this compound was linked to IONPs and Sanazole, and the obtained nanosystem displayed a reducing effect on hypoxic tumor volume in mice. Finally, essential oils have been bound to IONPs to improve their stabilization and reduce their volatility. Such nanostructures can be incorporated on the surface of catheters or into wound dressing materials in order to decrease microbial adherence and biofilm-associated infections.

4.3. Immunosuppressives

High concentrations of immunosuppressants may generate serious secondary complications in patients with transplants or autoimmune diseases. To minimize this problem, a nanosystem composed by silica (SI)-coated IONPs was formulated to act as a carrier of mycophenolic acid (MPA), the main component of the immunosuppressive mycophenolate mofetil. MPA was bound to the SI-coated IONPs by means of hydrophobic interactions, and the resulting nanosystem was biocompatible at the concentration of 0.56 mg/L, with capacity of transporting up to 30% of MPA’s weight. At this concentration, the IONPs-SI-MPA nanosystem was able to reduce the secretion of human interleukin 2 and tumor necrosis factor-α, indicating the activation of immune cells. Despite the 10-fold lower MPA supply when compared to other studies, this nanosystem promoted a similar efficacy in cytokine upregulation.

4.4. Anticonvulsants

Nanotechnology has also generated a novel and non-invasive approach for the treatment of temporal lobe epilepsy associated with pharmacological resistance. A nanosystem composed by anti-interleukin-(IL)-1β monoclonal antibody (1-β mAb) covalently attached to IONPs functionalized with PEG was developed and injected into the caudal vein of rats with acute temporal lobe-induced epilepsy. The MRI revealed a greater number of IONPs-anti (IL)-1β mAb-PEG in the epileptogenic tissues with respect to IONPs alone and the control group (saline solution), demonstrating a higher neuroprotective effect of the nanosystem. The effect of SI-coated IONPs loaded with the antiepileptic phenytoin (PHT) was also analyzed in an in vivo model assessing drug resistant convulsions. IONPs were previously coated with SI to avoid oxidation and improve stability. Thereafter, PTH was bound to SI-coated IONPs via adsorption, forming a nanosystem capable of carrying around 250 μg of PHT per 100 mg of nanoparticles. After administration of 3-mercaptopropionic acid (3MPA) in rats to induce convulsions associated with P-gliprotein cerebral overexpression, the IONPs-SI-PHT nanosystem was able to significantly increase the afterdischarge threshold values compared to the group of rats receiving pure saline solution, indicating its potential to reduce the neural excitability and the incidence of convulsion.

4.5. Anti-Inflammatories

The hydrophobic anti-inflammatory Ketoprofen (KTF) was encapsulated with IONPs, polypyrrole (PPL) and PEG to determine its release profile. For nanoparticles without PEG, the encapsulation efficiency of 20% KTF’s weight was 98%, ratifying the high binding capacity of the drug, which had its complete release after three hours in phosphate-buffered saline solution. Electrostatic interactions between the positively charged PPL and the negatively charged KTF probably facilitated encapsulation, while PEG stabilized the IONPs by simple adsorption. Jia et al. coupled IONPs and hyaluronic acid (AH) to a furan-functionalized dexamethasone peptide (GQPGK), aiming to target the system to adipose tissue defect sites. This dexamethasone peptide was attached to the nanostrutures via covalent bonds, and the IONPs-AH-GQPGK nanosystem presented the desired adipogenic effect on co-culture of human adipose derived stem cells, evidencing great potential for application in adipose regeneration therapies. In turn, IONPs also showed potential for acting as carrier of prednisolone to the cochlea. Intratympanic administration of these nanoparticles in conjunction with prednisolone did not promote severe injury in rats, which highlights the possibility of developing alternative nanocomposites for the treatment of auditory disorders.

4.6. Antibiotics

The emergence of highly resistant bacterial strains and the reduced alternatives to conventional antibiotics has aroused interest in the design of antibiotic-carrier nanosystems. IONPs functionalized with CS have been used as carriers of streptomycin. As a physical mixture, this antibiotic showed a rapid release (20 min) in phosphate-buffered saline, while in the form of a nanosystem its full release was completed only after 350 min, indicating the ability of IONPs to act in controlled-release systems.

Different groups of antibiotics (rifamycin, anthracycline, fluoroquinolone, tetracycline and cephalosporin) were bound by physical adsorption to silver nanoparticles (Ag)-loaded IONPs. It is believed that Ag (positively charged) interacts electrostatically with the IONPs, allowing linking of these antibiotics. Similarly, rifampicin, doxycycline, cefotaxime, and ceftriaxone were also attached to IONPs decorated with Ag, and the mechanisms of association varied for each type of antibiotic, including electrostatic binding with negative sites and hydrogen bonding. Synthesis using the green sonication-assisted procedure was tested for the conception of the nanosystem IONPs-Ag-rifampicin. The adsorption of rifampicin was evaluated at different Ag concentrations (5.3, 7.7, 10.1, 15.1 mass%) in the IONPs-Ag nanocomposite, and the lowest and highest adsorption occurred for Ag at 5.3 and 7.7 mass%, respectively.

Other models of therapeutic resources have also been studied, including IONPs-ciprofloxacin nanosystem, which may be functionalized with lactose particles. Furthermore, nanosystems composed by amikacin, amoxicillin, bacitracin, cefotaxime, erythromycin, gentamicin, kanamycin, neomycin, penicillin, polymyxin, streptomycin and vancomycin directly coupled to IONPs (i.e., without involving a shell coating) have been investigated.

4.7. Antifungals

Fungal diseases are opportunistic infections that often affect immunocompromised patients and, if not properly treated, can be fatal. Since Nystatin (NYS) is one of the most commonly used fungicides, Hussein-Al-Ali et al. prepared a nanosystem composed by IONPs, CS and NYS. The authors demonstrated that the release profile of NYS in a physical mixture of these isolated compounds lasted about 20 min, compared to 1800 min of the IONPs-CS-NYS nanosystem. This difference can be explained by the electrostatic interaction between NYS (negatively charged) and CS (positively charged), by which it can be inferred that the IONPs-CS-NYS nanosystem was able to generate a controlled release of NYS. Ketoconazole and amphotericin B are other antifungal drugs that have been tested in the development of magnetic nanosystems in order to decrease their side effects and improve antifungal action. Ketoconazole was coupled to epoxy-functionalized IONPs immobilized with HSA, and its binding mechanism occurred via hydrophobic interaction, while amphotericin B was directly bound to IONPs by a reaction between amine and aldehyde groups, respectively from the antifungal drug and IONPs.

5. Antimicrobial Activity of IONPs-Based Nanosystems

Studies suggest that the potential of magnetic nanoparticles to generate microbial toxicity is due to a series of interactions, including membrane depolarization with consequent impairment of cell integrity, production of reactive oxygen species (ROS) with lipid peroxidation and DNA damage, and release of metal ions that affect cellular homeostasis and protein coordination (Figure 3).

The antimicrobial potential of nanosystems has been evaluated against microorganisms in the planktonic state or forming biofilms, whose stage of development can affect the nanoparticles’ activity. The minimum inhibitory concentration (MIC) of the IONPs-amoxicillin nanosystem on Staphylococcus aureus and Escherichia coli planktonic cells was shown to be 3 to 4 times lower than the antibiotic alone. This nanosystem was also able to decrease the initial adhesion of those bacteria to polystyrene during the first 24 h of biofilm formation. In turn, the IONPs-CS-streptomycin nanosystem exhibited a more significant effect on Gram-negative microorganisms than on Gram-positive.

Aiming to potentiate antibiotics such as rifampicin, doxycyclin, ceftriaxone and cefotaxime, studies proposed their linking to 1.6% Ag-decorated IONPs. While IONPs alone did not prevent the growth of Bacillus pumilus, small inhibition halos (≤2 mm) were observed for IONPs-Ag, IONPs-Ag-ceftriaxone and IONPs-Ag-cefotaxime nanosystems. Furthermore, halos around 20 mm were found for IONPs-Ag-rifampicin and IONPs-Ag-doxycyclin. For S. aureus, only the IONPs-Ag-rifampicin, IONPs-Ag-doxycycline and IONPs-Ag-ceftriaxone nanosystems were effective, producing inhibition halos ranging from 10 to 24 mm. Furthermore, the IONPs-SI-Ag-vancomycin nanostructure was more effective than free vancomycin in inactivating strains of E. coli and methicillin-resistant S. aureus. Differences in the employed antibiotic concentrations may help to explain the results obtained. Finally, higher silver concentrations (5–10%) attached to IONPs and rifampicin were able to impair the growth of Streptococcus salivarius and S. aureus, but the same trend was not found for Pseudomonas fluorescens and B. pumilus, indicating that the effect of the nanocarrier is species-dependent. The increase in Ag concentration also improved the antibacterial properties against S. salivarius and S. aureus, amplifying the action spectrum of the antibiotic.

The incorporation of IONPs-based nanosystems into medical devices has shown promising results regarding the inhibition of microbial colonization. Catheter surfaces coated with essential oils-loaded IONPs decreased initial cell adhesion of S. aureus and Klebsiella pneumoniae, with a lesser effect on more mature stages of biofilm formation. In turn, coating of textile fibers of wound dressings with patchouli essential oil-attached IONPs was effective in reducing the number of S. aureus biofilm cells. Still concerning natural compounds, gallic acid-coated IONPs was shown to exhibit similar antimicrobial effects compared to ampicillin, streptomycin and nystatin against E. coli, Bacillus substilis and Aspergillus niger, respectively.

Despite the positive outcomes described above, conflicting results were reported for other nanosystems. While a nanosystem composed by IONPs, spray-dried lactose (SDL) and ciprofloxacin was shown to decrease the total biomass and metabolic activity of Pseudomonas aeruginosa biofilms (with an enhanced effect promoted by a magnetic field), the IONPs-ciprofloxacin nanosystem did not exhibit antimicrobial effects against E. coli, P. aeruginosa, methicillin-sensitive S. aureus, methicillin-resistant S. aureus, Streptococcus pneumoniae, vancomycin-sensitive Enterococcus faecalis, vancomycin-resistant E. faecalis, Acinetobacter baumannii, Proteus mirabilis, K. pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus epidermidis, Enterobacter aerogenes, Citrobacter freundii, and Enterobacter cloacae tested in the planktonic state or forming biofilms. Unfavorable results were also reported for P. aeruginosa, in which stimulation of biofilm formation was promoted by IONPs.

Drug carriers have also been tested as alternatives to combat the resistance of oral biofilms to commercially available drugs. Chlorhexidine (CHX), an antimicrobial agent used to control oral biofilms, was shown to be more effective when bound to IONPs in reducing biofilm biomass of S. aureus, E. faecalis and Candida albicans, in comparison with the drug applied alone. Moreover, CHX particles functionalized with IONPs inhibited the growth of Porphyromonas gingivalis and, when incorporated into HEMA-UDMA resin discs, revealed a CHX release kinetics influenced by magnetic field.

It is believed that nanoparticles have the ability to adsorb and penetrate into biofilms due to their physicochemical characteristics, such as surface charge, hydrophobicity and high surface area ratio by volume. Positively charged and neutral IONPs promoted higher reduction of cells of Streptococus mutans biofilms with respect to negatively charged counterparts, highlighting the influence of the surface properties of magnetic nanoparticles on their antibiofilm activity. Furthermore, IONPs have a good performance as catalysts, being nominated as catalytic IONPs (IONPs-CAT) or nanozymes. IONPs-CAT in association with H2O2 showed an enhanced antimicrobial effect on S. mutans biofilms compared to its counterpart without H2O2 in vitro. Under in vivo conditions, IONPs-CAT attenuated caries initiation and the severity of lesions, while H2O2 alone did not exhibit considerable effects, showing the potential of the IONPs in combating dental caries.

Besides drugs with antibacterial action, the association of IONPs with antifungal agents has shown to promote a significant effect on different microbial species. When amphotericin B and NYS were coupled to IONPs, the antifungal effect of the resulting nanosystems was potentiated in comparison with the free drugs on Candida spp.. In addition, CS-coated IONPs loaded with NYS promoted reductions of 1.3, 35.0, 99.0 and 99.9% in the number of cultivable cells of S. aureus, E. coli, P. aeruginosa and C. albicans, respectively, despite free NYS promoted a greater inhibition halo for C. albicans compared to the IONPs-CS-NYS nanosystem and the IONPs alone. Miconazole (MCZ), another conventional antifungal agent used for the treatment of oral candidiasis, has also been incorporated in CS-coated IONPs (Figure 4A). This new nanosystem showed a higher ability in disrupting dual-species biofilms of C. albicans and C. glabrata (Figure 4D) with respect to MCZ alone in vitro (Figure 4C), as evident by a less compact structure composed by a lower number of cell layers partially covering the surface (Figure 4D).

6. IONPs Toxicity

Conflicting evidence regarding the toxicity of IONPs has been reported in in vitro and in vivo studies. Factors inherent to nanosystems involving IONPs tend to directly interfere with their toxicity. For instance, changes in nanoparticle size and shape were shown to play an important role on cell toxicity, with rod-shaped or nano-sized IONPs being more toxic than sphere-shaped and micrometric particles, respectively. The configuration of the nanosystem can also influence IONPs toxicity. A Janus microsphere encapsulating mesenchymal stem cells (MSC) and IONPs in two different compartments was proven to facilitate the magnetization and movement of the microspheres (due to the higher load capacity of IONPs), and to reduce cell toxicity, since the IONPs’ derived toxic chemicals were isolated from the MSC compartment. Furthermore, the surface charge of IONPs may affect cell cytotoxicity and genotoxicity. Positively charged IONPs were shown to be more toxic, since they undergo nonspecific interactions and adsorptive endocytosis with the negatively charged cell membrane, thus increasing their intracellular accumulation and affecting cell membrane integrity. Other factors such as concentration, type of coating, form of administration, as well as the cell line may explain the different results for IONPs toxicity, as shown in Table 1.

6.1. Mechanisms of IONPs Toxicity

The toxicity of IONPs for different cell lines may be partially explained by the production of ROS, which causes cellular oxidative stress. When uptaken by cells via endocytosis, IONPs tend to accumulate in the lysosomes and are degraded in iron ions (Figure 3). In theory, the ions could cross the membranes and reach regions such as the cell nucleus and mitochondria, reacting with hydrogen peroxide and oxygen, thus generating ROS (Figure 3).

Despite oxidative stress is the most well-studied hypothesis of toxicity and cell damage, iron overload caused by exposure to IONPs can also generate serious deleterious effects and lead to cell death. On the other hand, magnetite was shown to be responsible for increasing the level of lipid peroxidation and decreasing antioxidant enzymes of human lung alveolar epithelial cells (A-549), displaying a concentration-dependent toxicity in vitro. In addition, a high dose of IONPs (with consequent iron excess) promoted elevated lipid metabolism, breakage of iron homeostasis and exacerbated loss of liver functions, being considered a risk factor for cirrhosis in a mice-model study.

6.2. Influence of Coatings on IONPs Toxicity

The surface coating of IONPs is a widely used procedure in order to make these nanoparticles biocompatible and non-toxic, supposedly due to lower number of oxidative sites, with consequent less DNA damage. In this sense, a well referenced in vitro study showed that uncoated IONPs produced greater toxicity for rat fibroblast cells when compared to nanoparticles coated with polyvinyl alcohol, due to changes in the protein functions and cellular ion balance caused by gas vesicles after exposure to uncoated particles. Additionally, uncoated IONPs were shown to increase intracellular density (greater ROS production), which might lead to relevant morphological cellular alterations, whereas protein-coated IONPs reached densities capable of causing tolerable changes. Also, the use of lauric acid, protein corona of BSA, or dextran as shells for IONPs did not promote genotoxic effects on human granulosa cells.

Coating with polymers and essential oils can also reduce the toxic effects of IONPs. PLGA-functionalized IONPs were able to reduce the destructive effects on lysosomes, mitochondria, golgi body and endoplasmic reticulum compared with uncoated nanoparticles, which induced the cells to autophagy. In turn, IONPs functionalized with patchouli essential oil promoted low cytotoxicity on mammalian cells and good biodistribution after intraperitoneal injection in mice.

Despite the remarkable advantages of IONPs coating, some divergences have been reported in the literature. Previous data showed that the coating of IONPs with D-mannose or poly-l-lysine was not able to prevent their toxicity in murine neural stem cells, as these nanoparticles demonstrated negative effects on the mithocondrial homeostasis. This emphasizes the importance of conducting additional tests other than cell viability for a more complete assessment of the toxic effects of these nanosystems.

7. Conclusions and Perspectives

Microorganisms resistant to conventional treatments evolve faster than the creation of new drugs and antibiotics. Within this context, IONPs bear great potential for use in nanosystems capable of overcoming the physical barriers of the microbial biofilm matrix in delivering the drugs directly to the target. The next steps consist in further exploring the magnetic properties of IONPs to improve the drug effect using lower concentrations, thus reducing side effects and toxicity.

The various methods of synthesis have allowed the creation of nanoparticles with different sizes, structures, dispersions and surface modifications. However, as wide variations have been reported among different research protocols, a direct comparison of the results obtained cannot be done. This aspect points out to the need for a refinement/standardization of protocols of synthesis and functionalization prior to in vivo testing, aiming to produce nanoparticles with adequate stability, size-control, biocompatibility and bioavailability.

Despite the growing body of scientific evidence on the use of IONPs in drug delivery systems, not all relevant drugs of medical/dental interest have been investigated, either alone or in combination with IONPs. In this sense, the conception of novel IONPs-based nanosystems able to carry multiple drugs simultaneously, and with adequate release control on the target tissues could be beneficial in several clinical situations. These include the prevention/control of diseases associated with multiple microorganisms (e.g., bacteria and fungi), as well as conditions that require different categories of drugs (e.g., anti-inflammatories, antibiotics and antifungals).

Finally, regarding the applicability of IONPs-based nanosystems, most of clinical trials conducted so far have focused on MRI, so that clinical assessment of applications other than MRI is expected in the near future. For such purpose, large and industrial-scale production of IONPs-based nanosystems is an important challenge to be overcome.

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    Ramírez-Cando L.J., De Simone U., Coccini T. Toxicity evaluation of iron oxide (Fe3O4) nanoparticles on human neuroblastoma-derived SH-SY5Y cell line. J. Nanosci. Nanotechnol. 2017;17:203-211.

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  73. 73.

    Chomoucka J., Drbohlavova J., Huska D., Adam V., Kizek R., Hubalek J. Magnetic nanoparticles and targeted drug delivering. Pharm. Res. 2010;62:144-149.

    Not in our library10.1016/j.phrs.2010.01.014

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    Makadia H.K., Siegel S.J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3:1377-1397.

    Not in our library10.3390/polym3031377

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    Houchin M.L., Topp E.M. Physical properties of PLGA films during polymer degradation. J. Appl. Polym. Sci. 2009;114:2848-2854.

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    Abdalla M.O., Aneja R., Dean D., Rangari V., Russell A., Jaynes J., Yates C., Turner T. Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles. J. Magn. Magn. Mater. 2010;322:190-196.

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    Agnihotri S.A., Mallikarjuna N.N., Aminabhavi T.M. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J. Control. Release. 2004;100:5-28.

    Not in our library10.1016/j.jconrel.2004.08.010

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    Berscht P.C., Nies B., Liebendörfer A., Kreuter J. Incorporation of basic fibroblast growth factor into methylpyrrolidinone chitosan fleeces and determination of the in vitro release characteristics. Biomaterials. 1994;15:593-600.

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  79. 79.

    Arai K., Kinumaki T., Fujita T. Toxicity of chitosan. Bull. Tokai Reg. Fish. Lab. 1968;43:89-94.

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  80. 80.

    Nicol S. Life after death for empty shells: Crustacean fisheries create a mountain of waste shells, made of a strong natural polymer, chitin. Now chemists are helping to put this waste to some surprising uses. New Sci. 1991;129:46-48.

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  81. 81.

    Qi L., Xu Z., Jiang X., Hu C., Zou X. Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr. Res. 2004;339:2693-2700.

    Not in our library10.1016/j.carres.2004.09.007

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    Yang S.J., Shieh M.J., Lin F.H., Lou P.J., Peng C.L., Wei M.F., Yao C.J., Lai P.S., Young T.H. Colorectal cancer cell detection by 5-aminolaevulinic acid-loaded chitosan nano-particles. Cancer Lett. 2009;273:210-220.

    Not in our library10.1016/j.canlet.2008.08.014

  83. 83.

    Sun Y., Chen Z.L., Yang X.X., Huang P., Zhou X.P., Du X.X. Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy. Nanotechnology. 2009;20:135102.

    Not in our library10.1088/0957-4484/20/13/135102

  84. 84.

    Mathew T.V., Kuriakose S. Photochemical and antimicrobial properties of silver nanoparticle-encapsulated chitosan functionalized with photoactive groups. Mater. Sci. Eng. C Mater. Biol. Appl. 2013;33:4409-4415.

    Not in our library10.1016/j.msec.2013.06.037

  85. 85.

    Zhou W., Wang Y., Jian J., Song S. Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B. Int. J. Nanomed. 2013;8:3715-3728.

    Not in our library10.2147/ijn.s51186

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    Radulescu M., Ficai D., Oprea O., Ficai A., Andronescu E., Holban A.M. Antimicrobial chitosan based formulations with impact on different biomedical applications. Curr. Pharm. Biotechnol. 2015;16:128-136.

    Not in our library10.2174/138920101602150112151157

  87. 87.

    Onnainty R., Onida B., Páez P., Longhi M., Barresi A., Granero G. Targeted chitosan-based bionanocomposites for controlled oral mucosal delivery of chlorhexidine. Int. J. Pharm. 2016;509:408-418.

    Not in our library10.1016/j.ijpharm.2016.06.011

  88. 88.

    Li L., Chen D., Zhang Y., Deng Z., Ren X., Meng X., Tang F., Ren J., Zhang L. Magnetic and fluorescent multifunctional chitosan nanoparticles as a smart drug delivery system. Nanotechnology. 2007;18:405102.

    Not in our library10.1088/0957-4484/18/40/405102

  89. 89.

    Soares P.I., Machado D., Laia C., Pereira L.C., Coutinho J.T., Ferreira I.M., Novo C.M., Borges J.P. Thermal and magnetic properties of chitosan-iron oxide nanoparticles. Carbohydr. Polym. 2016;149:382-390.

    Not in our library10.1016/j.carbpol.2016.04.123

  90. 90.

    Gupta A.K., Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2005;26:3995-4021.

    Not in our library10.1016/j.biomaterials.2004.10.012

  91. 91.

    Prabaharan M. Review paper: Chitosan derivatives as promising materials for controlled drug delivery. J. Biomater. Appl. 2008;23:5-36.

    Not in our library10.1177/0885328208091562

  92. 92.

    Zhu A., Chan-Park M.B., Dai S., Li L. The aggregation behavior of O-carboxymethylchitosan in dilute aqueous solution. Colloids Surf. B Biointerfaces. 2005;43:143-149.

    Not in our library10.1016/j.colsurfb.2005.04.009

  93. 93.

    Saikia C., Hussain A., Ramteke A., Sharma H.K., Maji T.K. Carboxymethyl starch-chitosan-coated iron oxide magnetic nanoparticles for controlled delivery of isoniazid. J. Microencapsul. 2015;32:29-39.

    Not in our library10.3109/02652048.2014.940015

  94. 94.

    Soares P.I., Lochte F., Echeverria C., Pereira L.C., Coutinho J.T., Ferreira I.M., Novo C.M., Borges J.P. Thermal and magnetic properties of iron oxide colloids: Influence of surfactants. Nanotechnology. 2015;26:425704.

    Not in our library10.1088/0957-4484/26/42/425704

  95. 95.

    Wang Y., Wong J.F., Teng X., Lin X.Z., Yang H. “Pulling” nanoparticles into water: Phase transfer of oleic acid stabilized monodisperse nanoparticles into aqueous solutions of alpha-cyclodextrin. Nano Lett. 2003;3:7907-7911.

    Not in our library10.1021/nl034731j

  96. 96.

    Costa C., Brandão F., Bessa M.J., Costa S., Valdiglesias V., Kiliç G., Fernández-Bertólez N., Quaresma P., Pereira E., Pásaro E., et al. In vitro cytotoxicity of superparamagnetic iron oxide nanoparticles on neuronal and glial cells. Evaluation of nanoparticle interference with viability tests. J. Appl. Toxicol. 2016;36:361-372.

    Not in our library10.1002/jat.3213

  97. 97.

    Toropova Y.G., Golovkin A.S., Malashicheva A.B., Korolev D.V., Gorshkov A.N., Gareev K.G., Afonin M.V., Galagudza M.M. In vitro toxicity of FemOn, FemOn-SiO2 composite, and SiO2-FemOn core-shell magnetic nanoparticles. Int. J. Nanomed. 2017;12:593-603.

    Not in our library10.2147/ijn.s122580

  98. 98.

    Kandibanda S.R., Gundeboina N., Das S., Sunkara V.M. Synthesis, characterisation, cellular uptake and cytotoxicity of functionalised magnetic ruthenium (II) polypyridine complex core-shell nanocomposite. J. Photochem. Photobiol. B. 2018;178:270-276.

    Not in our library10.1016/j.jphotobiol.2017.10.037

  99. 99.

    Ma K., Wang Q., Rong Q., Zhang D., Cui S., Yang J. Preparation of magnetic carbon/Fe3O4 supported zero-valent iron composites and their application in Pb(II) removal from aqueous solutions. Water Sci. Technol. 2017;76:2680-2689.

    Not in our library10.2166/wst.2017.384

  100. 100.

    Ivashchenko O., Lewandowski M., Peplińska B., Jarek M., Nowaczyk G., Wiesner M., Załęski K., Babutina T., Warowicka A., Jurga S. Synthesis and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;55:343-359.

    Not in our library10.1016/j.msec.2015.05.023

  101. 101.

    Tamer U., Gündoğdu Y., Boyaci I.H., Pekmez K. Synthesis of magnetic core-shell Fe3O4-Au, nanoparticles for biomolecule immobilization and detection. J. Nanopart. Res. 2010;12:1187-1196.

    Not in our library10.1007/s11051-009-9749-0

  102. 102.

    Bisht G., Rayamajhi S., Kc B., Paudel S.N., Karna D., Shrestha B.G. Synthesis, characterization, and study of in vitro cytotoxicity of ZnO-Fe3O4 magnetic composite nanoparticles in human breast cancer cell line (MDA-MB-231) and mouse fibroblast (NIH 3T3). Nanoscale Res. Lett. 2016;11:537.

    Not in our library10.1186/s11671-016-1734-9

  103. 103.

    Rădulescu M., Andronescu E., Holban A.M., Vasile B.S., Iordache F., Mogoantă L., Mogoșanu G.D., Grumezescu A.M., Georgescu M., Chifiriuc M.C. Antimicrobial nanostructured bioactive coating based on Fe3O4 and patchouli oil for wound dressing. Metals. 2016;6:103.

    Not in our library10.3390/met6050103

  104. 104.

    Mu Q., Kievit F.M., Kant R.J., Lin G., Jeon M., Zhang M. Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells. Nanoscale. 2015;7:18010-18014.

    Not in our library10.1039/c5nr04867b

  105. 105.

    Jahanban-Esfahlan A., Dastmalchi S., Davaran S. A simple improved desolvation method for the rapid preparation of albumin nanoparticles. Int. J. Biol. Macromol. 2016;91:703-709.

    Not in our library10.1016/j.ijbiomac.2016.05.032

  106. 106.

    Nosrati H., Sefidi N., Sharafi A., Danafar H., Kheiri Manjili H. Bovine Serum Albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug. Bioorg. Chem. 2018;76:501-509.

    Not in our library10.1016/j.bioorg.2017.12.033

  107. 107.

    Thomas R.G., Unnithan A.R., Moon M.J., Surendran S.P., Batgerel T., Park C.H., Kim C.S., Jeong Y.Y. Electromagnetic manipulation enabled calcium alginate Janus microsphere for targeted delivery of mesenchymal stem cells. Int. J. Biol. Macromol. 2018;110:465-471.

    Not in our library10.1016/j.ijbiomac.2018.01.003

  108. 108.

    Hans M.L., Lowman A.M., Gogotsi Y. Nanoparticles for Drug Delivery. Nanomaterials Handbook. 2006;637-664.

    Not in our library

  109. 109.

    Pillai G. Nanomedicines for cancer therapy: An update of FDA approved and those under various stages of development. SOJ Pharm. Pharm. Sci. 2014;2:1-13.

    Not in our library10.15226/2374-6866/1/2/00109

  110. 110.

    Ebrahimi E., Akbarzadeh A., Abbasi E., Khandaghi A.A., Abasalizadeh F., Davaran S. Novel drug delivery system based on doxorubicin-encapsulated magnetic nanoparticles modified with PLGA-PEG 1000 copolymer. Artif. Cells Nanomed. Biotechnol. 2016;44:290-297.

    Not in our library10.3109/21691401.2014.944646

  111. 111.

    Nigam S., Bahadur D. Doxorubicin-loaded dendritic-Fe3O4 supramolecular nanoparticles for magnetic drug targeting and tumor regression in spheroid murine melanoma model. Nanomedicine. 2018;14:759-768.

    Not in our library10.1016/j.nano.2018.01.005

  112. 112.

    Abbasi Aval N., Pirayesh Islamian J., Hatamian M., Arabfirouzjaei M., Javadpour J., Rashidi M.R. Doxorubicin loaded large-pore mesoporous hydroxyapatite coated superparamagnetic Fe3O4 nanoparticles for cancer treatment. Int. J. Pharm. 2016;509:159-167.

    Not in our library10.1016/j.ijpharm.2016.05.046

  113. 113.

    Liang P.C., Chen Y.C., Chiang C.F., Mo L.R., Wei S.Y., Hsieh W.Y., Lin W.L. Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy. Int. J. Nanomed. 2016;11:2021-2037.

    Not in our library10.2147/ijn.s9413

  114. 114.

    Augustin E., Czubek B., Nowicka A.M., Kowalczyk A., Stojek Z., Mazerska Z. Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles. Toxicol. In Vitro. 2016;33:45-53.

    Not in our library10.1016/j.tiv.2016.02.009

  115. 115.

    Jurado R., Frączek P., Droetto M., Sánchez P., Valero E., Domínguez-Vera J.M., Gálvez N. Apomaghemite as a doxorubicin carrier for anticancer drug delivery. J. Inorg. Biochem. 2016;157:46-51.

    Not in our library10.1016/j.jinorgbio.2016.01.018

  116. 116.

    Montha W., Maneeprakorn W., Buatong N., Tang I.M., Pon-On W. Synthesis of doxorubicin-PLGA loaded chitosan stabilized (Mn, Zn)Fe2O4 nanoparticles: Biological activity and pH-responsive drug release. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;59:235-240.

    Not in our library10.1016/j.msec.2015.09.098

  117. 117.

    Mallick N., Anwar M., Asfer M., Mehdi S.H., Rizvi M.M., Panda A.K., Talegaonkar S., Ahmad F.J. Chondroitin sulfate-capped super-paramagnetic iron oxide nanoparticles as potential carriers of doxorubicin hydrochloride. Carbohydr. Polym. 2016;151:546-556.

    Not in our library10.1016/j.carbpol.2016.05.102

  118. 118.

    Nadeem M., Ahmad M., Akhtar M.S., Shaari A., Riaz S., Naseem S., Masood M., Saeed M.A. Magnetic properties of polyvinyl alcohol and doxorubicine loaded iron oxide nanoparticles for anticancer drug delivery applications. PLoS ONE. 2016;11:e0158084.

    Not in our library10.1371/journal.pone.0158084

  119. 119.

    Tarvirdipour S., Vasheghani-Farahani E., Soleimani M., Bardania H. Functionalized magnetic dextran-spermine nanocarriers for targeted delivery of doxorubicin to breast cancer cells. Int. J. Pharm. 2016;501:331-341.

    Not in our library10.1016/j.ijpharm.2016.02.012

  120. 120.

    Thorat N.D., Lemine O.M., Bohara R.A., Omri K., El Mir L., Tofail S.A. Superparamagnetic iron oxide nanocargoes for combined cancer thermotherapy and MRI applications. Phys. Chem. Chem. Phys. 2016;18:21331-21339.

    Not in our library10.1039/c6cp03430f

  121. 121.

    Wang Y., Zhao R., Wang S., Liu Z., Tang R. In vivo dual-targeted chemotherapy of drug resistant cancer by rationally designed nanocarrier. Biomaterials. 2016;75:71-81.

    Not in our library10.1016/j.biomaterials.2015.09.030

  122. 122.

    Nehate C., Aji Alex M.R., Kumar A., Koul V. Combinatorial delivery of superparamagnetic iron oxide nanoparticles (γ Fe2O3) and doxorubicin using folate conjugated redox sensitive multiblock polymeric nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;75:1128-1143.

    Not in our library10.1016/j.msec.2017.03.024

  123. 123.

    Wu L., Chen L., Liu F., Qi X., Ge Y., Shen S. Remotely controlled drug release based on iron oxide nanoparticles for specific therapy of cancer. Colloids Surf. B Biointerfaces. 2017;152:440-448.

    Not in our library10.1016/j.colsurfb.2017.01.015

  124. 124.

    Bekaroglu M.G., Isci Y., Isci S. Colloidal properties and in vitro evaluation of Hydroxy ethyl cellulose coated iron oxide particles for targeted drug delivery. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;78:847-853.

    Not in our library10.1016/j.msec.2017.04.030

  125. 125.

    Benyettou F., Alhashimi M., O’Connor M., Pasricha R., Brandel J., Traboulsi H., Mazher J., Olsen J.C., Trabolsi A. Sequential delivery of doxorubicin and zoledronic acid to breast cancer cells by CB[7]-modified iron oxide nanoparticles. ACS Appl. Mater. Interfaces. 2017;9:40006-40016.

    Not in our library10.1021/acsami.7b11423

  126. 126.

    Mosafer J., Teymouri M. Comparative study of superparamagnetic iron oxide/doxorubicin co-loaded poly (lactic-co-glycolic acid) nanospheres prepared by different emulsion solvent evaporation methods. Artif. Cells Nanomed. Biotechnol. 2017;46:1-10.

    Not in our library10.1080/21691401.2017.1362415

  127. 127.

    Mosafer J., Teymouri M., Abnous K., Tafaghodi M., Ramezani M. Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;72:123-133.

    Not in our library10.1016/j.msec.2016.11.053

  128. 128.

    Prabha G., Raj V. Sodium alginate-polyvinyl alcohol-bovin serum albumin coated Fe3O4 nanoparticles as anticancer drug delivery vehicle: Doxorubicin loading and in vitro release study and cytotoxicity to HepG2 and L02 cells. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;79:410-422.

    Not in our library10.1016/j.msec.2017.04.075

  129. 129.

    Islam M.S., Haque P., Rashid T.U., Khan M.N., Mallik A.K., Khan M.N., Khan M., Rahman M.M. Core-shell drug carrier from folate conjugated chitosan obtained from prawn shell for targeted doxorubicin delivery. J. Mater. Sci. Mater. Med. 2017;28:55.

    Not in our library10.1007/s10856-017-5859-x

  130. 130.

    Mu X., Zhang F., Kong C., Zhang H., Zhang W., Ge R., Liu Y., Jiang J. EGFR-targeted delivery of DOX-loaded Fe3O4@ polydopamine multifunctional nanocomposites for MRI and antitumor chemo-photothermal therapy. Int. J. Nanomed. 2017;12:2899-2911.

    Not in our library10.2147/ijn.s131418

  131. 131.

    Arachchige M.P., Laha S.S., Naik A.R., Lewis K.T., Naik R., Jena B.P. Functionalized nanoparticles enable tracking the rapid entry and release of doxorubicin in human pancreatic cancer cells. Micron. 2017;92:25-31.

    Not in our library10.1016/j.micron.2016.10.005

  132. 132.

    Pan C., Liu Y., Zhou M., Wang W., Shi M., Xing M., Liao W. Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment. Int. J. Nanomed. 2018;13:1119-1137.

    Not in our library10.2147/ijn.s147464

  133. 133.

    Dutta B., Shetake N.G., Barick B.K., Barick K.C., Pandey B.N., Priyadarsini K.I., Hassan P.A. pH sensitive surfactant-stabilized Fe3O4 magnetic nanocarriers for dual drug delivery. Colloids Surf. B Biointerfaces. 2018;162:163-171.

    Not in our library10.1016/j.colsurfb.2017.11.054

  134. 134.

    Ji F., Zhang K., Li J., Gu Y., Zhao J., Zhang J. A Dual pH/magnetic responsive nanocarrier based on PEGylated Fe3O4 nanoparticles for doxorubicin delivery. J. Nanosci. Nanotechnol. 2018;18:4464-4470.

    Not in our library10.1166/jnn.2018.15275

  135. 135.

    Shelat R., Chandra S., Khanna A. Detailed toxicity evaluation of beta-cyclodextrin coated iron oxide nanoparticles for biomedical applications. Int. J. Biol. Macromol. 2018;110:357-365.

    Not in our library10.1016/j.ijbiomac.2017.09.067

  136. 136.

    Akilo O.D., Choonara Y.E., Strydom A.M., du Toit L.C., Kumar P., Modi G., Pillay V. An in vitro evaluation of a carmustine-loaded Nano-co-Plex for potential magnetic-targeted intranasal delivery to the brain. Int. J. Pharm. 2016;500:196-209.

    Not in our library10.1016/j.ijpharm.2016.01.043

  137. 137.

    Freeman A.C., Platt S.R., Holmes S., Kent M., Robinson K., Howerth E., Eagleson J., Bouras A., Kaluzova M., Hadjipanayis C.G. Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas. J. Neurooncol. 2018.

    Not in our library10.1007/s11060-018-2764-1

  138. 138.

    Tseng S.H., Chou M.Y., Chu I.M. Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy. Int. J. Nanomed. 2015;10:3663-3685.

    Not in our library10.2147/ijn.s80134

  139. 139.

    Kaluzova M., Bouras A., Machaidze R., Hadjipanayis C.G. Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles. Oncotarget. 2015;6:8788-8806.

    Not in our library10.18632/oncotarget.3554

  140. 140.

    Shahabadi N., Falsafi H., Mansouri K. Improving antiproliferative effect of the anticancer drug cytarabine on human promyelocytic leukemia cells by coating on Fe3O4@SiO2 nanoparticles. Colloids Surf. B Biointerfaces. 2016;141:213-222.

    Not in our library10.1016/j.colsurfb.2016.01.054

  141. 141.

    Liu M.C., Jin S.F., Zheng M., Wang Y., Zhao P.L., Tang D.T., Chen J., Lin J.Q., Wang X.H., Zhao P. Daunomycin-loaded superparamagnetic iron oxide nanoparticles: Preparation, magnetic targeting, cell cytotoxicity, and protein delivery research. J. Biomater. Appl. 2016;31:261-272.

    Not in our library10.1177/0885328216654425

  142. 142.

    Al-Jamal K.T., Bai J., Wang J.T., Protti A., Southern P., Bogart L., Heidari H., Li X., Cakebread A., Asker D., et al. Magnetic drug targeting: Preclinical in vivo studies, mathematical modeling, and extrapolation to humans. Nano Lett. 2016;16:5652-5660.

    Not in our library10.1021/acs.nanolett.6b02261

  143. 143.

    Nagesh P.K., Johnson N.R., Boya V.K., Chowdhury P., Othman S.F., Khalilzad-Sharghi V., Hafeez B.B., Ganju A., Khan S., Behrman S.W., et al. PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer. Colloids Surf. B Biointerfaces. 2016;144:8-20.

    Not in our library10.1016/j.colsurfb.2016.03.071

  144. 144.

    Rao Y.F., Chen W., Liang X.G., Huang Y.Z., Miao J., Liu L., Lou Y., Zhang X.G., Wang B., Tang R.K., et al. Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: Cancer therapy by circumventing the skin barrier. Small. 2015;11:239-247.

    Not in our library10.1002/smll.201400775

  145. 145.

    Alupei L., Peptu C.A., Lungan A.M., Desbrieres J., Chiscan O., Radji S., Popa M. New hybrid magnetic nanoparticles based on chitosan-maltose derivative for antitumor drug delivery. Int. J. Biol. Macromol. 2016;92:561-572.

    Not in our library10.1016/j.ijbiomac.2016.07.058

  146. 146.

    Prabha G., Raj V. Formation and characterization of b-cyclodextrin (b-CD)–polyethyleneglycol (PEG)–polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug. Biomed. Pharmacother. 2016;80:173-182.

    Not in our library10.1016/j.biopha.2016.03.015

  147. 147.

    Esmaelbeygi E., Khoei S., Khoee S., Eynali S. Role of iron oxide core of polymeric nanoparticles in the thermosensitivity of colon cancer cell line HT-29. Int. J. Hyperth. 2015;31:489-497.

    Not in our library10.3109/02656736.2015.1035766

  148. 148.

    Eynali S., Khoei S., Khoei S., Esmaelbeygi E. Evaluation of the cytotoxic effects of hyperthermia and 5-fluorouracil loaded magnetic nanoparticles on human colon cancer cell line HT-29. Int. J. Hyperth. 2016;1-33.

    Not in our library10.1080/02656736.2016.1243260

  149. 149.

    Hashemi-Moghaddam H., Kazemi-Bagsangani S., Jamili M., Zavareh S. Evaluation of magnetic nanoparticles coated by 5-fluorouracil imprinted polymer for controlled drug delivery in mouse breast cancer model. Int. J. Pharm. 2016;497:228-238.

    Not in our library10.1016/j.ijpharm.2015.11.040

  150. 150.

    Sağir T., Huysal M., Durmus Z., Kurt B.Z., Senel M., Isık S. Preparation and in vitro evaluation of 5-flourouracil loaded magnetite–zeolite nanocomposite (5-FU-MZNC) for cancer drug delivery applications. Biomed. Pharmacother. 2016;77:182-189.

    Not in our library10.1016/j.biopha.2015.12.025

  151. 151.

    Şanlı O., Kahraman A., Kondolot Solak E., Olukman M. Preparation of magnetite-chitosan/methylcellulose nanospheres by entrapment and adsorption techniques for targeting the anti-cancer drug 5-fluorouracil. Artif. Cells Nanomed. Biotechnol. 2016;44:950-959.

    Not in our library10.3109/21691401.2015.1008502

  152. 152.

    Tuncelli G., Ay A.N., Zümreoglu-Karan B. 5-Fluorouracil intercalated iron oxide@layered double hydroxide core-shell nano-composites with isotropic and anisotropic architectures for shape-selective drug delivery applications. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;55:562-568.

    Not in our library10.1016/j.msec.2015.06.001

  153. 153.

    Asadi N., Annabi N., Mostafavi E., Anzabi M., Khalilov R., Saghfi S., Mehrizadeh M., Akbarzadeh A. Synthesis, characterization and in vitro evaluation of magnetic nanoparticles modified with PCL-PEG-PCL for controlled delivery of 5FU. Artif. Cells Nanomed. Biotechnol. 2018.

    Not in our library10.1080/21691401.2018.1439839

  154. 154.

    Mu Q., Lin G., Patton V.K., Wang K., Press O.W., Zhang M. Gemcitabine and chlorotoxin conjugated iron oxide nanoparticles for glioblastoma therapy. J. Mater. Chem. B Mater. Biol. Med. 2016;4:32-36.

    Not in our library10.1039/c5tb02123e

  155. 155.

    Aires A., Ocampo S.M., Simões B.M., Josefa Rodríguez M., Cadenas J.F., Couleaud P., Spence K., Latorre A., Miranda R., Somoza Á., et al. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells. Nanotechnology. 2016;27:065103.

    Not in our library10.1088/0957-4484/27/6/065103

  156. 156.

    Ferreira R.V., Martins T.M., Goes A.M., Fabris J.D., Cavalcante L.C., Outon L.E., Domingues R.Z. Termosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy. Nanotechnology. 2016;27:085105.

    Not in our library10.1088/0957-4484/27/8/085105

  157. 157.

    Hamarat Sanlıer S., Yasa M., Cihnioglu A.O., Abdulhayoglu M., Yılmaz H., Ak G. Development of gemcitabine-adsorbed magnetic gelatin nanoparticles for targeted drug delivery in lung cancer. Artif. Cells Nanomed. Biotechnol. 2016;44:943-949.

    Not in our library10.3109/21691401.2014.1001493

  158. 158.

    Jaidev L.R., Chellappan D.R., Bhavsar D.V., Ranganathan R., Sivanantham B., Subramanian A., Sharma U., Jagannathan N.R., Krishnan U.M., Sethuraman S. Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer. Acta Biomater. 2017;49:422-433.

    Not in our library10.1016/j.actbio.2016.11.053

  159. 159.

    Lin J., Li Y., Li Y., Wu H., Yu F., Zhou S., Xie L., Luo F., Lin C., Hou Z. Drug/dye-loaded, multifunctional PEG-chitosan-iron oxide nanocomposites for methotraxate synergistically self-targeted cancer therapy and dual model imaging. ACS Appl. Mater. Interfaces. 2015;7:11908-11920.

    Not in our library10.1021/acsami.5b01685

  160. 160.

    Jahangiri S., Akbarzadeh A. Preparation and in vitro evaluation of Methotrexate-loaded magnetic nanoparticles modified with biocompatible copolymers. Artif. Cells Nanomed. Biotechnol. 2016;44:1733-1740.

    Not in our library10.3109/21691401.2015.1090443

  161. 161.

    Nosrati H., Salehiabar M., Davaran S., Danafar H., Manjili H.K. Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells. Drug Dev. Ind. Pharm. 2017;1-9.

    Not in our library10.1080/03639045.2017.1417422

  162. 162.

    Barar J., Kafil V., Majd M.H., Barzegari A., Khani S., Johari-Ahar M., Asgari D., Coukos G., Omidi Y. Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells. J. Nanobiotechnol. 2015;13:26.

    Not in our library10.1186/s12951-015-0083-7

  163. 163.

    Cicha I., Scheffler L., Ebenau A., Lyer S., Alexiou C., Goppelt-Struebe M. Mitoxantrone-loaded superparamagnetic iron oxide nanoparticles as drug carriers for cancer therapy: Uptake and toxicity in primary human tubular epithelial cells. Nanotoxicology. 2016;10:557-566.

    Not in our library10.3109/17435390.2015.1095364

  164. 164.

    Hornung A., Poettler M., Friedrich R.P., Zaloga J., Unterweger H., Lyer S., Nowak J., Odenbach S., Alexiou C., Janko C. Treatment efficiency of free and nanoparticle-loaded mitoxantrone for magnetic drug targeting in multicellular tumor spheroids. Molecules. 2015;20:18016-18030.

    Not in our library10.3390/molecules201018016

  165. 165.

    Zaloga J., Pöttler M., Leitinger G., Friedrich R.P., Almer G., Lyer S., Baum E., Tietze R., Heimke-Brinck R., Mangge H., et al. Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting. Eur. J. Pharm. Biopharm. 2016;101:152-162.

    Not in our library10.1016/j.ejpb.2016.01.017

  166. 166.

    Hsiao M.H., Mu Q., Stephen Z.R., Fang C., Zhang M. Hexanoyl-chitosan-PEG copolymer coated iron oxide nanoparticles for hydrophobic drug delivery. ACS Macro Lett. 2015;4:403-407.

    Not in our library10.1021/acsmacrolett.5b00091

  167. 167.

    Jeon H., Kim J., Lee Y.M., Kim J., Choi H.W., Lee J., Park H., Kang Y., Kim I.S., Lee B.H., et al. Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system. J. Control Release. 2016;231:68-76.

    Not in our library10.1016/j.jconrel.2016.01.006

  168. 168.

    Lee J.Y., Carugo D., Crake C., Owen J., de Saint Victor M., Seth A., Coussios C., Stride E. Nanoparticle-loaded protein-polymer nanodroplets for improved stability and conversion efficiency in ultrasound imaging and drug delivery. Adv. Mater. 2015;27:5484-5492.

    Not in our library10.1002/adma.201502022

  169. 169.

    Nguyen D.H., Lee J.S., Choi J.H., Park K.M., Lee Y., Park K.D. Hierarchical self-assembly of magnetic nanoclusters for theranostics: Tunable size, enhanced magnetic resonance imagability, and controlled and targeted drug delivery. Acta Biomater. 2016;35:109-117.

    Not in our library10.1016/j.actbio.2016.02.020

  170. 170.

    Ruggiero M.R., Crich S.G., Sieni E., Sgarbossa P., Forzan M., Cavallari E., Stefania R., Dughiero F., Aime S. Magnetic hyperthermia efficiency and (1)H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles. Nanotechnology. 2016;27:285104.

    Not in our library10.1088/0957-4484/27/28/285104

  171. 171.

    Swain A.K., Pradhan L., Bahadur D. Polymer Stabilized Fe3O4-graphene as an amphiphilic drug carrier for thermo-chemotherapy of cancer. ACS Appl. Mater. Interfaces. 2015;7:8013-8022.

    Not in our library10.1021/acsami.5b02536

  172. 172.
    Enhanced tumor targeting effects of a novel paclitaxel-loaded polymer: PEG–PCCL-modified magnetic iron oxide nanoparticles · 2017
    Not checked
  173. 173.

    Patra S., Roy E., Karfa P., Kumar S., Madhuri R., Sharma P.K. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment. ACS Appl. Mater. Interfaces. 2015;7:9235-9246.

    Not in our library10.1021/acsami.5b01786

  174. 174.

    Prabha G., Raj V. Preparation and characterization of chitosan-Polyethylene glycol-polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles as carrier system: Drug loading and in vitro drug release study. J. Biomed. Mater. Res. B Appl. Biomater. 2016;104:808-816.

    Not in our library10.1002/jbm.b.33637

  175. 175.

    Mancarella S., Greco V., Baldassarre F., Vergara D., Maffia M., Leporatti S. Polymer-coated magnetic nanoparticles for curcumin delivery to cancer cells. Macromol. Biosci. 2015;15:1365-1374.

    Not in our library10.1002/mabi.201500142

  176. 176.

    Unterweger H., Subatzus D., Tietze R., Janko C., Poettler M., Stiegelschmitt A., Schuster M., Maake C., Boccaccini A.R., Alexiou C. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy. Int. J. Nanomed. 2015;10:6985-6996.

    Not in our library10.2147/ijn.s92336

  177. 177.

    Sreeja S., Krishnan Nair C.K. Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle—Berberine complexes in a mouse model. Life Sci. 2018;195:71-80.

    Not in our library10.1016/j.lfs.2017.12.036

  178. 178.

    Bilcu M., Grumezescu A.M., Oprea A.E., Popescu R.C., Mogoșanu G.D., Hristu R., Stanciu G.A., Mihailescu D.F., Lazar V., Bezirtzoglou E., et al. Efficiency of vanilla, patchouli and ylang ylang essential oils stabilized by iron oxide@C14 nanostructures against bacterial adherence and biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae clinical strains. Molecules. 2014;19:17943-17956.

    Not in our library10.3390/molecules191117943

  179. 179.

    Sollinger H.W. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. renal transplant mycophenolate mofetil study group. Transplantation. 1995;60:225-232.

    Not in our library10.1097/00007890-199508000-00003

  180. 180.

    Hwang J., Lee E., Kim J., Seo Y., Lee K.H., Hong J.W., Gilad A.A., Park H., Choi J. Effective delivery of immunosuppressive drug molecules by silica coated iron oxide nanoparticles. Colloids Surf. B Biointerfaces. 2016;142:290-296.

    Not in our library10.1016/j.colsurfb.2016.01.040

  181. 181.

    He X., Smeets R.L., Koenen H.J., Vink P.M., Wagenaars J., Boots A.M., Joosten I. Mycophenolic acid-mediated suppression of human CD4+ T cells: More than mere guanine nucleotide deprivation. Am. J. Transpl. 2011;11:439-449.

    Not in our library10.1111/j.1600-6143.2010.03413.x

  182. 182.

    Liu Z., Yuan X., Luo Y., He Y., Jiang Y., Chen Z.K., Sun E. Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood. Cytokine. 2009;45:141-147.

    Not in our library10.1016/j.cyto.2008.12.003

  183. 183.

    Fu T., Kong Q., Sheng H., Gao L. Value of functionalized superparamagnetic iron oxide nanoparticles in the diagnosis and treatment of acute temporal lobe epilepsy on MRI. Neural Plast. 2016;2016:1-12.

    Not in our library10.1155/2016/2412958

  184. 184.

    Rosillo-de la Torre A., Zurita-Olvera L., Orozco-Suárez S., Garcia Casillas P.E., Salgado-Ceballos H., Luna-Bárcenas G., Rocha L. Phenytoin carried by silica core iron oxide nanoparticles reduces the expression of pharmacoresistant seizures in rats. Nanomedicine. 2015;10:3563-3577.

    Not in our library10.2217/nnm.15.173

  185. 185.

    Lazarowski A., Ramos A.J., García-Rivello H., Brusco A., Girardi E. Neuronal and glial expression of the multidrug resistance gene product in an experimental epilepsy model. Cell. Mol. Neurobiol. 2004;24:77-85.

    Not in our library10.1023/b:cemn.0000012726.43842.d2

  186. 186.

    Attia M.F., Anton N., Khan I.U., Serra C.A., Messaddeq N., Jakhmola A., Vecchione R., Vandamme T. One-step synthesis of iron oxide polypyrrole nanoparticles encapsulating ketoprofen as model of hydrophobic drug. Int. J. Pharm. 2016;508:61-70.

    Not in our library10.1016/j.ijpharm.2016.04.073

  187. 187.

    Jia Y., Fan M., Chen H., Miao Y., Xing L., Jiang B., Cheng Q., Liu D., Bao W., Qian B., et al. Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering. J. Colloid Interface Sci. 2015;458:293-299.

    Not in our library10.1016/j.jcis.2015.07.062

  188. 188.

    Lafond J.F., Shimoji M., Ramaswamy B., Shukoor M.I., Malik P., Shapiro B., Depireux D.A. Middle ear histopathology following magnetic delivery to the cochlea of prednisolone-loaded iron oxide nanoparticles in rats. Toxicol. Pathol. 2018;46:101-106.

    Not in our library10.1177/0192623317732028

  189. 189.

    Hussein-Al-Ali S.H., El Zowalaty M.E., Hussein M.Z., Ismail M., Webster T.J. Synthesis, characterization, controlled release, and antibacterial studies of a novel streptomycin chitosan magnetic nanoantibiotic. Int. J. Nanomed. 2014;16:549-557.

    Not in our library10.2147/ijn.s53079

  190. 190.

    El Zowalaty M.E., Hussein-Al-Ali S.H., Husseiny M.I., Geilich B.M., Webster T.J., Hussein M.Z. The ability of streptomycin-loaded chitosan-coated magnetic nanocomposites to possess antimicrobial and antituberculosis activities. Int. J. Nanomed. 2015;10:3269-3274.

    Not in our library10.2147/ijn.s74469

  191. 191.

    Ivashchenko O., Jurga-Stopa J., Coy E., Peplinska B., Pietralik Z., Jurga S. Fourier transform infrared and Raman spectroscopy studies on magnetite/Ag/antibiotic nanocomposites. Appl. Surf. Sci. 2016;364:400-409.

    Not in our library10.1016/j.apsusc.2015.12.149

  192. 192.

    Ivashchenko O., Coy E., Peplinska B., Jarek M., Lewandowski M., Załęski K., Warowicka A., Wozniak A., Babutina T., Jurga-Stopa J., et al. Influence of silver content on rifampicin adsorptivity for magnetite/Ag/rifampicin nanoparticles. Nanotechnology. 2017;28:055603.

    Not in our library10.1088/1361-6528/28/5/055603

  193. 193.

    Masadeh M.M., Karasneh G.A., Al-Akhras M.A., Albiss B.A., Aljarah K.M., Al-Azzam S.I., Alzoubi K.H. Cerium oxide and iron oxide nanoparticles abolish the antibacterial activity of ciprofloxacin against gram positive and gram negative biofilm bacteria. Cytotechnology. 2015;67:427-435.

    Not in our library10.1007/s10616-014-9701-8

  194. 194.

    Bandara H.M., Nguyen D., Mogarala S., Osiñski M., Smyth H.D. Magnetic fields suppress Pseudomonas aeruginosa biofilms and enhance ciprofloxacin activity. Biofouling. 2015;31:443-457.

    Not in our library10.1080/08927014.2015.1055326

  195. 195.

    Istrate C.M., Holban A.M., Grumezescu A.M., Mogoantă L., Mogoşanu G.D., Savopol T., Moisescu M., Iordache M., Vasile B.S., Kovacs E. Iron oxide nanoparticles modulate the interaction of different antibiotics with cellular membranes. Rom. J. Morphol. Embryol. 2014;55:849-856.

    Not in our library

  196. 196.

    Hussein-Al-Ali S.H., El Zowalaty M.E., Kura A.U., Geilich B., Fakurazi S., Webster T.J., Hussein M.Z. Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite. Biomed. Res. Int. 2014;2014:651831.

    Not in our library10.1155/2014/651831

  197. 197.

    Maltas E., Ozmen M., Yildirimer B., Kucukkolbasi S., Yildiz S. Interaction between ketoconazole and human serum albumin on epoxy modified magnetic nanoparticles for drug delivery. J. Nanosci. Nanotechnol. 2013;13:6522-6528.

    Not in our library10.1166/jnn.2013.7742

  198. 198.

    Niemirowicz K., Durnaś B., Tokajuk G., Głuszek K., Wilczewska A.Z., Misztalewska I., Mystkowska J., Michalak G., Sodo A., Wątek M., et al. Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics. Nanomedicine. 2016;12:2395-2404.

    Not in our library10.1016/j.nano.2016.07.006

  199. 199.

    Pelgrift R.Y., Friedman A.J. Nanotechnology as a therapeutic tool to combat microbial resistance. Adv. Drug Deliv. Rev. 2013;65:1803-1815.

    Not in our library10.1016/j.addr.2013.07.011

  200. 200.

    Pan X., Redding J.E., Wiley P.A., Wen L., McConnell J.S., Zhang B. Mutagenicity evaluation of metal oxide nanoparticles by the bacterial reverse mutation assay. Chemosphere. 2010;79:113-116.

    Not in our library10.1016/j.chemosphere.2009.12.056

  201. 201.

    Saleh N.B., Chambers B., Aich N., Plazas-Tuttle J., Phung-Ngoc H.N., Kirisits M.J. Mechanistic lessons learned from studies of planktonic bacteria with metallic nanomaterials: Implications for interactions between nanomaterials and biofilm bacteria. Front. Microbiol. 2015;6:677.

    Not in our library10.3389/fmicb.2015.00677

  202. 202.

    Grumezescu A.M., Gestal M.C., Holban A.M., Grumezescu V., Vasile B.S., Mogoantă L., Iordache F., Bleotu C., Mogoșanu G.D. Biocompatible Fe3O4 increases the efficacy of amoxicillin delivery against Gram-positive and Gram-negative bacteria. Molecules. 2014;19:5013-5027.

    Not in our library10.3390/molecules19045013

  203. 203.

    Wang C., Zhang K., Zhou Z., Li Q., Shao L., Hao R.Z., Xiao R., Wang S. Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents. Int. J. Nanomed. 2017;12:3077-3094.

    Not in our library10.2147/ijn.s132570

  204. 204.

    Shah S.T., A Yehya W., Saad O., Simarani K., Chowdhury Z., A Alhadi A., Al-Ani L.A. Surface functionalization of iron oxide nanoparticles with gallic acid as potential antioxidant and antimicrobial agents. Nanomaterials. 2017;7:306.

    Not in our library10.3390/nano7100306

  205. 205.

    Borcherding J., Baltrusaitis J., Chen H., Stebounova L., Wu C.M., Rubasinghege G., Mudunkotuwa I.A., Caraballo J.C., Zabner J., Grassian V.H., et al. Iron oxide nanoparticles induce Pseudomonas aeruginosa growth, induce biofilm formation, and inhibit antimicrobial peptide function. Environ. Sci. Nano. 2014;1:123-132.

    Not in our library10.1039/c3en00029j

  206. 206.

    Haney C., Rowe J.J., Robinson J.B. Spions increase biofilm formation by Pseudomonas aeruginosa. J. Biomater. Nanobiotechnol. 2012;3:508-518.

    Not in our library10.4236/jbnb.2012.324052

  207. 207.

    Tokajuk G., Niemirowicz K., Deptula P., Piktel E., Ciesluk M., Wilczewska A.Z., Dąbrowski J.R., Bucki R. Use of magnetic nanoparticles as a drug delivery system to improve chlorhexidine antimicrobial activity. Int. J. Nanomed. 2017;12:7833-7846.

    Not in our library10.2147/ijn.s140661

  208. 208.

    Luo D., Shahid S., Hasan S.M., Whiley R., Sukhorukov G.B., Cattell M.J. Controlled release of chlorhexidine from a HEMA-UDMA resin using a magnetic field. Dent. Mater. 2018;34:764-775.

    Not in our library10.1016/j.dental.2018.02.001

  209. 209.

    Morones J.R., Elechiguerra J.L., Camacho A., Holt K., Kouri J.B., Ramírez J.T., Yacaman M.J. The bactericidal effect of silver nanoparticles. Nanotechnology. 2005;16:2346-2353.

    Not in our library10.1088/0957-4484/16/10/059

  210. 210.

    Nel A.E., Mädler L., Velegol D., Xia T., Hoek E.M., Somasundaran P., Klaessig F., Castranova V., Thompson M. Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater. 2009;8:543-557.

    Not in our library10.1038/nmat2442

  211. 211.
    Relating the Surface Properties of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to Their Bactericidal Effect towards a Biofilm of Streptococcus mutans. · 2016
    Not checked
  212. 212.

    Gao L., Liu Y., Kim D., Li Y., Hwang G., Naha P.C., Cormode D.P., Koo H. Nanocatalysts promote Streptococcus mutans biofilm matrix degradation and enhance bacterial killing to suppress dental caries in vivo. Biomaterials. 2016;101:272-284.

    Not in our library10.1016/j.biomaterials.2016.05.051

  213. 213.

    Valdiglesias V., Kiliç G., Costa C., Fernández-Bertólez N., Pásaro E., Teixeira J.P., Laffon B. Effects of iron oxide nanoparticles: Cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity. Environ. Mol. Mutagen. 2015;56:125-148.

    Not in our library10.1002/em.21909

  214. 214.
    In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles · 2015
    No notice
  215. 215.

    Sonmez E., Aydin E., Turkez H., Özbek E., Togar B., Meral K., Çetin D., Cacciatore I., Di Stefano A. Cytotoxicity and genotoxicity of iron oxide nanoparticles: An in vitro biosafety study. Arch. Biol. Sci. 2016;68:41-50.

    Not in our library10.2298/abs141218006s

  216. 216.

    Xu H.L., Mao K.L., Huang Y.P., Yang J.J., Xu J., Chen P.P., Fan Z.L., Zou S., Gao Z.Z., Yin J.Y., et al. Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects. Nanoscale. 2016;8:14222-14236.

    Not in our library10.1039/c6nr02448c

  217. 217.

    Lee J.H., Ju J.E., Kim B.I., Pak P.J., Choi E.K., Lee H.S., Chung N. Rod-shaped iron oxide nanoparticles are more toxic than sphere-shaped nanoparticles to murine macrophage cells. Environ. Toxicol. Chem. 2014;33:2759-2766.

    Not in our library10.1002/etc.2735

  218. 218.

    Hong S.C., Lee J.H., Lee J., Kim H.Y., Park J.Y., Cho J., Lee J., Han D.W. Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups. Int. J. Nanomed. 2011;6:3219-3231.

    Not in our library10.2147/ijn.s26355

  219. 219.
    Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings · 2018
    No notice
  220. 220.

    Valdiglesias V., Fernández-Bertólez N., Kiliç G., Costa C., Costa S., Fraga S., Bessa M.J., Pásaro E., Teixeira J.P., Laffon B. Are iron oxide nanoparticles safe? Current knowledge and future perspectives. J. Trace Elem. Med. Biol. 2016;38:53-63.

    Not in our library10.1016/j.jtemb.2016.03.017

  221. 221.

    Bellusci M., La Barbera A., Padella F., Mancuso M., Pasquo A., Grollino M.G., Leter G., Nardi E., Cremisini C., Giardullo P., et al. Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process. Int. J. Nanomed. 2014;9:1919-1929.

    Not in our library10.2147/ijn.s56394

  222. 222.

    Hajikarimi Z., Khoei S., Khoee S., Mahdavi S.R. Evaluation of the cytotoxic effects of PLGA coated iron oxide nanoparticles as a carrier of 5-fluorouracil and mega-voltage X-ray radiation in DU145 prostate cancer cell line. IEEE Trans. Nanobiosci. 2014;13:403-408.

    Not in our library10.1109/tnb.2014.2328868

  223. 223.

    Raji M.A., Amara M., Amoabediny G., Tajik P., Barin A., Magierowski S., Ghafar-Zadeh E. Cytotoxicity of synthesized iron oxide nanoparticles: Toward novel biomarkers of colon cancer. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2014;2014:6179-6182.

    Not in our library10.1109/embc.2014.6945040

  224. 224.

    Calero M., Gutiérrez L., Salas G., Luengo Y., Lázaro A., Acedo P., Morales M.P., Miranda R., Villanueva A. Efficient and safe internalization of magnetic iron oxide nanoparticles: Two fundamental requirements for biomedical applications. Nanomedicine. 2014;10:733-743.

    Not in our library10.1016/j.nano.2013.11.010

  225. 225.

    Sun B., Liu R., Ye N., Xiao Z.D. Comprehensive evaluation of microRNA expression profiling reveals the neural signaling specific cytotoxicity of superparamagnetic iron oxide nanoparticles (SPIONs) through N-methyl-d-aspartate receptor. PLoS ONE. 2015;10:e0121671.

    Not in our library10.1371/journal.pone.0121671

  226. 226.

    Sadeghi L., Tanwir F., Yousefi Babadi V. In vitro toxicity of iron oxide nanoparticle: Oxidative damages on Hep G2 cells. Exp. Toxicol. Pathol. 2015;67:197-203.

    Not in our library10.1016/j.etp.2014.11.010

  227. 227.

    Yalcin S., Khodadust R., Unsoy G., Garip I.C., Mumcuoglu Z.D., Gunduz U. Synthesis and characterization of polyhydroxybutyrate coated magnetic nanoparticles: Toxicity analyses on different cell lines. Synth. React. Inorg. Met.-Org. Nano-Met. Chem. 2015;45:700-708.

    Not in our library10.1080/15533174.2013.831448

  228. 228.

    Cheng K.K., Chan P.S., Fan S., Kwan S.M., Yeung K.L., Wang Y.X., Chow A.H., Wu E.X., Baum L. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI). Biomaterials. 2015;44:155-172.

    Not in our library10.1016/j.biomaterials.2014.12.005

  229. 229.

    Comănescu M.V., Mocanu M.A., Anghelache L., Marinescu B., Dumitrache F., Bădoi A.D., Manda G. Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery setting—Preliminary preclinical study. Rom. J. Morphol. Embryol. 2015;56:691-696.

    Not in our library

  230. 230.

    Couto D., Sousa R., Andrade L., Leander M., Lopez-Quintela M.A., Rivas J., Freitas P., Lima M., Porto G., Porto B., et al. Polyacrylic acid coated and non-coated iron oxide nanoparticles are not genotoxic to human T lymphocytes. Toxicol. Lett. 2015;234:67-73.

    Not in our library10.1016/j.toxlet.2015.02.010

  231. 231.

    Ghasempour S., Shokrgozar M.A., Ghasempour R., Alipour M. Investigating the cytotoxicity of iron oxide nanoparticles in in vivo and in vitro studies. Exp. Toxicol. Pathol. 2015;67:509-515.

    Not in our library10.1016/j.etp.2015.07.005

  232. 232.

    Liao S.H., Liu C.H., Bastakoti B.P., Suzuki N., Chang Y., Yamauchi Y., Lin F.H., Wu K.C. Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia. Int. J. Nanomed. 2015;10:3315-3328.

    Not in our library10.2147/ijn.s68719

  233. 233.

    Magdolenova Z., Drlickova M., Henjum K., Rundén-Pran E., Tulinska J., Bilanicova D., Pojana G., Kazimirova A., Barancokova M., Kuricova M., et al. Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. Nanotoxicology. 2015;9:44-56.

    Not in our library10.3109/17435390.2013.847505

  234. 234.

    Venkatesan K., Rajan Babu D., Kavya Bai M.P., Supriya R., Vidya R., Madeswaran S., Anandan P., Arivanandhan M., Hayakawa Y. Structural and magnetic properties of cobalt-doped iron oxide nanoparticles prepared by solution combustion method for biomedical applications. Int. J. Nanomed. 2015;10:189-198.

    Not in our library10.2147/ijn.s82210

  235. 235.

    Paolini A., Guarch C.P., Ramos-López D., de Lapuente J., Lascialfari A., Guari Y., Larionova J., Long J., Nano R. Rhamnose-coated superparamagnetic iron-oxide nanoparticles: An evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity. J. Appl. Toxicol. 2016;36:510-520.

    Not in our library10.1002/jat.3273

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    Bhandari R., Gupta P., Dziubla T., Hilt J.Z. Single step synthesis, characterization and applications of curcumin functionalized iron oxide magnetic nanoparticles. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;67:59-64.

    Not in our library10.1016/j.msec.2016.04.093

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    Friedrich R.P., Zaloga J., Schreiber E., Tóth I.Y., Tombácz E., Lyer S., Alexiou C. Tissue plasminogen activator binding to superparamagnetic iron oxide nanoparticle-covalent versus adsorptive approach. Nanoscale Res. Lett. 2016;11:297.

    Not in our library10.1186/s11671-016-1521-7

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    Park J., Kadasala N.R., Abouelmagd S.A., Castanares M.A., Collins D.S., Wei A., Yeo Y. Polymer-iron oxide composite nanoparticles for EPR-independent drug delivery. Biomaterials. 2016;101:285-295.

    Not in our library10.1016/j.biomaterials.2016.06.007

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    Rajiv S., Jerobin J., Saranya V., Nainawat M., Sharma A., Makwana P., Gayathri C., Bharath L., Singh M., Kumar M., et al. Comparative cytotoxicity and genotoxicity of cobalt (II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro. Hum. Exp. Toxicol. 2016;35:170-183.

    Not in our library10.1177/0960327115579208

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    Jarockyte G., Daugelaite E., Stasys M., Statkute U., Poderys V., Tseng T.C., Hsu S.H., Karabanovas V., Rotomskis R. Accumulation and toxicity of superparamagnetic iron oxide nanoparticles in cells and experimental animals. Int. J. Mol. Sci. 2016;17:1193.

    Not in our library10.3390/ijms17081193

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    Song X., Gu X., Sun H., Fu C., Zhang Y., Dong P. Biomimetic modification and in vivo safety assessment of superparamagnetic iron oxide nanoparticles. J. Nanosci. Nanotechnol. 2016;16:4100-4107.

    Not in our library10.1166/jnn.2016.11640

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    Huang Y., Mao K., Zhang B., Zhao Y. Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;70:763-771.

    Not in our library10.1016/j.msec.2016.09.052

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    Zhang H., Xia J., Pang X., Zhao M., Wang B., Yang L., Wan H., Wu J., Fu S. Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2017;73:537-543.

    Not in our library10.1016/j.msec.2016.12.116

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    Sohrabijam Z., Saeidifar M., Zamanian A. Enhancement of magnetofection efficiency using chitosan coated superparamagnetic iron oxide nanoparticles and calf thymus DNA. Colloids Surf. B Biointerfaces. 2017;152:169-175.

    Not in our library10.1016/j.colsurfb.2017.01.028

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    Moise S., Céspedes E., Soukup D., Byrne J.M., El Haj A.J., Telling N.D. The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles. Sci. Rep. 2017;7:39922.

    Not in our library10.1038/srep39922

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    Patel S., Jana S., Chetty R., Thakore S., Singh M., Devkar R. Toxicity evaluation of magnetic iron oxide nanoparticles reveals neuronal loss in chicken embryo. Drug Chem. Toxicol. 2017;27:1-8.

    Not in our library10.1080/01480545.2017.1413110

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    Salimi M., Sarkar S., Fathi S., Alizadeh A.M., Saber R., Moradi F., Delavari H. Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice. Int. J. Nanomed. 2018;13:1483-1493.

    Not in our library10.2147/ijn.s157293

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    Shevtsov M., Nikolaev B., Marchenko Y., Yakovleva L., Skvortsov N., Mazur A., Tolstoy P., Ryzhov V., Multhoff G. Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs). Int. J. Nanomed. 2018;13:1471-1482.

    Not in our library10.2147/ijn.s152461

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    Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling · 2009
    No notice
  250. 250.

    Singh N., Jenkins G.J., Asadi R., Doak S.H. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev. 2010;1:5358.

    Not in our library10.3402/nano.v1i0.5358

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    Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation · 2017
    No notice
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    Dwivedi S., Siddiqui M.A., Farshori N.N., Ahamed M., Musarrat J., Al-Khedhairy A.A. Synthesis, characterization and toxicological evaluation of iron oxide nanoparticles in human lung alveolar epithelial cells. Colloids Surf. B Biointerfaces. 2014;122:209-215.

    Not in our library10.1016/j.colsurfb.2014.06.064

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    Wei Y., Zhao M., Yang F., Mao Y., Xie H., Zhou Q. Iron overload by superparamagnetic iron oxide nanoparticles is a high risk factor in cirrhosis by a systems toxicology assessment. Sci. Rep. 2016;6:29110.

    Not in our library10.1038/srep29110

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    Mahmoudi M., Simchi A., Imani M., Milani A.S., Stroeve P. An in vitro study of bare and poly(ethylene glycol)-co-fumaratecoated superparamagnetic iron oxide nanoparticles: A new toxicity identification procedure. Nanotechnology. 2009;20:225104.

    Not in our library10.1088/0957-4484/20/22/225104

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    Mahmoudi M., Simchi A., Imani M., Shokrgozar M.A., Milani A.S., Häfeli U.O., Stroeve P. A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. Colloids Surf. B Biointerfaces. 2010;75:300-309.

    Not in our library10.1016/j.colsurfb.2009.08.044

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    Sanganeria P., Sachar S., Chandra S., Bahadur D., Ray P., Khanna A. Cellular internalization and detailed toxicity analysis of protein-immobilized iron oxide nanoparticles. J. Biomed. Mater. Res. B Appl. Biomater. 2015;103:125-134.

    Not in our library10.1002/jbm.b.33178

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    Pöttler M., Staicu A., Zaloga J., Unterweger H., Weigel B., Schreiber E., Hofmann S., Wiest I., Jeschke U., Alexiou C., et al. Genotoxicity of superparamagnetic iron oxide nanoparticles in granulosa cells. Int. J. Mol. Sci. 2015;16:26280-26290.

    Not in our library10.3390/ijms161125960

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    Zhang X., Zhang H., Liang X., Zhang J., Tao W., Zhu X., Chang D., Zeng X., Liu G., Mei L. Iron oxide nanoparticles induce autophagosome accumulation through multiple mechanisms: Lysosome impairment, mitochondrial damage, and ER stress. Mol. Pharm. 2016;13:2578-2587.

    Not in our library10.1021/acs.molpharmaceut.6b00405

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    Pongrac I.M., Pavičić I., Milić M., Brkić Ahmed L., Babič M., Horák D., Vinković Vrček I., Gajović S. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles. Int. J. Nanomed. 2016;11:1701-1715.

    Not in our library10.2147/ijn.s102730

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