Cell Membrane-Coated Mimics: A Methodological Approach for Fabrication, Characterization for Therapeutic Applications, and Challenges for Clinical Translation

Abstract

Cell membrane-coated (CMC) mimics are micro/nanosystems that combine an isolated cell membrane and a template of choice to mimic the functions of a cell. The design exploits its physicochemical and biological properties for therapeutic applications. The mimics demonstrate excellent biological compatibility, enhanced biointerfacing capabilities, physical, chemical, and biological tunability, ability to retain cellular properties, immune escape, prolonged circulation time, and protect the encapsulated drug from degradation and active targeting. These properties and the ease of adapting them for personalized clinical medicine have generated a significant research interest over the past decade. This review presents a detailed overview of the recent advances in the development of cell membrane-coated (CMC) mimics. The primary focus is to collate and discuss components, fabrication methodologies, and the significance of physiochemical and biological characterization techniques for validating a CMC mimic. We present a critical analysis of the two main components of CMC mimics: the template and the cell membrane and mapped their use in therapeutic scenarios. In addition, we have emphasized on the challenges associated with CMC mimics in their clinical translation. Overall, this review is an up to date toolbox that researchers can benefit from while designing and characterizing CMC mimics.

References 415

1. 1.

   Latourte A.; Kloppenburg M.; Richette P. Emerging Pharmaceutical Therapies for Osteoarthritis. Nat. Rev. Rheumatol. 2020, 16, 673–688..

   Not in our library10.1038/s41584-020-00518-6

2. 2.

   Sanders J. M.; Monogue M. L.; Jodlowski T. Z.; Cutrell J. B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. J. Am. Med. Assoc. 2020, 323, 1824–1836..

   Not in our library10.1001/jama.2020.6019

3. 3.

   Sahin U.; Kariko K.; Tureci O. mRNA-Based Therapeutics-Developing a New Class of Drugs. Nat. Rev. Drug Discovery 2014, 13, 759–780..

   Not in our library10.1038/nrd4278

4. 4.

   Van de Glind E. M.; Van Enst W. A.; Van Munster B. C.; Olde Rikkert M. G.; Scheltens P.; Scholten R. J.; Hooft L. Pharmacological Treatment of Dementia: A Scoping Review of Systematic Reviews. Dementia Geriatr. Cognit. Disord. 2013, 36, 211–228..

   Not in our library10.1159/000353892

5. 5.

   Talsky A.; Pacione L. R.; Shaw T.; Wasserman L.; Lenny A. M.; Verma A.; Hurwitz G.; Waxman R.; Morgan A.; Bhalerao S. Pharmacological Interventions for Traumatic Brain Injury. B. C. Med. J. 2011, 53, 26–31.

   Not in our library

6. 6.

   Sartori S. B.; Singewald N. Novel Pharmacological Targets in Drug Development for the Treatment of Anxiety and Anxiety-Related Disorders. Pharmacol. Ther. 2019, 204, 107402–107434..

   Not in our library10.1016/j.pharmthera.2019.107402

7. 7.

   Chidambaram M.; Manavalan R.; Kathiresan K. Nanotherapeutics to Overcome Conventional Cancer Chemotherapy Limitations. J. Pharm. Pharm. Sci. 2011, 14, 67–77..

   Not in our library10.18433/j30c7d

8. 8.

   Veiseh O.; Tang B. C.; Whitehead K. A.; Anderson D. G.; Langer R. Managing Diabetes with Nanomedicine: Challenges and Opportunities. Nat. Rev. Drug Discovery 2015, 14, 45–57..

   Not in our library10.1038/nrd4477

9. 9.

   Nel A. E. Transformational Impact of Nanomedicine: Reconciling Outcome with Promise. Nano Lett. 2020, 20, 5601–5603..

   Not in our library10.1021/acs.nanolett.0c02738

10. 10.

    Hadjidemetriou M.; Kostarelos K. Nanomedicine: Evolution of the Nanoparticle Corona. Nat. Nanotechnol. 2017, 12, 288–290..

    Not in our library10.1038/nnano.2017.61

11. 11.

    Cai P.; Zhang X.; Wang M.; Wu Y. L.; Chen X. Combinatorial Nano-Bio Interfaces. ACS Nano 2018, 12, 5078–5084..

    Not in our library10.1021/acsnano.8b03285

12. 12.

    Nienhaus K.; Wang H.; Nienhaus G. U. Nanoparticles for Biomedical Applications: Exploring and Exploiting Molecular Interactions at the Nano-Bio Interface. Mater. Today Adv. 2020, 5, 100036–100055..

    Not in our library10.1016/j.mtadv.2019.100036

13. 13.

    Mura S.; Nicolas J.; Couvreur P. Stimuli-Responsive Nanocarriers for Drug Delivery. Nat. Mater. 2013, 12, 991–1003..

    Not in our library10.1038/nmat3776

14. 14.

    Karimi M.; Ghasemi A.; Sahandi Zangabad P.; Rahighi R.; Moosavi Basri S. M.; Mirshekari H.; Amiri M.; Shafaei Pishabad Z.; Aslani A.; Bozorgomid M.; Ghosh D.; Beyzavi A.; Vaseghi A.; Aref A. R.; Haghani L.; Bahrami S.; Hamblin M. R. Smart Micro/Nanoparticles in Stimulus-Responsive Drug/Gene Delivery Systems. Chem. Soc. Rev. 2016, 45, 1457–1501..

    Not in our library10.1039/c5cs00798d

15. 15.

    Parodi A.; Molinaro R.; Sushnitha M.; Evangelopoulos M.; Martinez J. O.; Arrighetti N.; Corbo C.; Tasciotti E. Bio-Inspired Engineering of Cell and Virus-Like Nanoparticles for Drug Delivery. Biomaterials 2017, 147, 155–168..

    Not in our library10.1016/j.biomaterials.2017.09.020

16. 16.

    Moncalvo F.; Martinez Espinoza M. I.; Cellesi F. Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies. Front. Bioeng. Biotechnol. 2020, 8, 89.

    Not in our library10.3389/fbioe.2020.00089

17. 17.
    Stealth Coating of Nanoparticles in Drug-Delivery Systems · 2020

    No notice
18. 18.
    Targeted Intracellular Delivery of Antibodies: The State of the Art · 2018

    No notice
19. 19.
    Targeted drug delivery for cancer therapy: the other side of antibodies · 2012

    No notice
20. 20.
    Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy · 2020

    No notice
21. 21.

    Guan B.; Zhang X. Aptamers As Versatile Ligands for Biomedical and Pharmaceutical Applications. Int. J. Nanomed. 2020, 15, 1059–1071..

    Not in our library10.2147/ijn.s237544

22. 22.

    Lian Z.; Ji T. Functional Peptide-Based Drug Delivery Systems. J. Mater. Chem. B 2020, 8, 6517–6529..

    Not in our library10.1039/d0tb00713g

23. 23.
    Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies · 2020

    No notice
24. 24.

    Zhuang C.; Guan X.; Ma H.; Cong H.; Zhang W.; Miao Z. Small Molecule-Drug Conjugates: A Novel Strategy for Cancer-Targeted Treatment. Eur. J. Med. Chem. 2019, 163, 883–895..

    Not in our library10.1016/j.ejmech.2018.12.035

25. 25.

    Ekladious I.; Colson Y. L.; Grinstaff M. W. Polymer-Drug Conjugate Therapeutics: Advances, Insights and Prospects. Nat. Rev. Drug Discovery 2019, 18, 273–294..

    Not in our library10.1038/s41573-018-0005-0

26. 26.

    Merkel T. J.; Jones S. W.; Herlihy K. P.; Kersey F. R.; Shields A. R.; Napier M.; Luft J. C.; Wu H.; Zamboni W. C.; Wang A. Z.; Bear J. E.; DeSimone J. M. Using Mechanobiological Mimicry of Red Blood Cells to Extend Circulation Times of Hydrogel Microparticles. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 586–591..

    Not in our library10.1073/pnas.1010013108

27. 27.

    Palange A. L.; Palomba R.; Rizzuti I. F.; Ferreira M.; Decuzzi P. Deformable Discoidal Polymeric Nanoconstructs for the Precise Delivery of Therapeutic and Imaging Agents. Mol. Ther. 2017, 25, 1514–1521..

    Not in our library10.1016/j.ymthe.2017.02.012

28. 28.

    Schoonen L.; van Hest J. C. Compartmentalization Approaches in Soft Matter Science: From Nanoreactor Development to Organelle Mimics. Adv. Mater. 2016, 28, 1109–1128..

    Not in our library10.1002/adma.201502389

29. 29.

    Mason A. F.; Yewdall N. A.; Welzen P. L. W.; Shao J.; van Stevendaal M.; van Hest J. C. M.; Williams D. S.; Abdelmohsen L. Mimicking Cellular Compartmentalization in a Hierarchical Protocell through Spontaneous Spatial Organization. ACS Cent. Sci. 2019, 5, 1360–1365..

    Not in our library10.1021/acscentsci.9b00345

30. 30.

    Balasubramanian V.; Poillucci A.; Correia A.; Zhang H.; Celia C.; Santos H. A. Cell Membrane-Based Nanoreactor to Mimic the Bio-Compartmentalization Strategy of a Cell. ACS Biomater. Sci. Eng. 2018, 4, 1471–1478..

    Not in our library10.1021/acsbiomaterials.7b00944

31. 31.

    Zhang X.; Tanner P.; Graff A.; Palivan C. G.; Meier W. Mimicking the Cell Membrane with Block Copolymer Membranes. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 2293–2318..

    Not in our library10.1002/pola.26000

32. 32.

    Peetla C.; Stine A.; Labhasetwar V. Biophysical Interactions with Model Lipid Membranes: Applications in Drug Discovery and Drug Delivery. Mol. Pharmaceutics 2009, 6, 1264–1276..

    Not in our library10.1021/mp9000662

33. 33.

    Lo C.; Bhardwaj K.; Marculescu R. Towards Cell-Based Therapeutics: A Bio-Inspired Autonomous Drug Delivery System. Nano Commun. Netw 2017, 12, 25–33..

    Not in our library10.1016/j.nancom.2017.01.006

34. 34.

    Petrenko V. A. Autonomous Self-Navigating Drug-Delivery Vehicles: From Science Fiction to Reality. Ther. Delivery 2017, 8, 1063–1107..

    Not in our library10.4155/tde-2017-0086

35. 35.

    Large D. E.; Soucy J. R.; Hebert J.; Auguste D. T. Advances in Receptor-Mediated, Tumor-Targeted Drug Delivery. Adv. Therap. 2019, 2, 1800091–1800117..

    Not in our library10.1002/adtp.201800091

36. 36.

    Karimi M.; Sahandi Zangabad P.; Baghaee-Ravari S.; Ghazadeh M.; Mirshekari H.; Hamblin M. R. Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light. J. Am. Chem. Soc. 2017, 139, 4584–4610..

    Not in our library10.1021/jacs.6b08313

37. 37.

    Chowdhury A.; Kunjiappan S.; Panneerselvam T.; Somasundaram B.; Bhattacharjee C. Nanotechnology and Nanocarrier-Based Approaches on Treatment of Degenerative Diseases. Int. Nano Lett. 2017, 7, 91–122..

    Not in our library10.1007/s40089-017-0208-0

38. 38.
    Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation · 2018

    No notice
39. 39.

    Dimov N.; Kastner E.; Hussain M.; Perrie Y.; Szita N. Formation and Purification of Tailored Liposomes for Drug Delivery Using a Module-Based Micro Continuous-Flow System. Sci. Rep. 2017, 7, 12045–12057..

    Not in our library10.1038/s41598-017-11533-1

40. 40.

    Gothwal A.; Khan I.; Gupta U. Polymeric Micelles: Recent Advancements in the Delivery of Anticancer Drugs. Pharm. Res. 2016, 33, 18–39..

    Not in our library10.1007/s11095-015-1784-1

Cited by papers we hold 2

• Recent advances of engineering cell membranes for nanomedicine delivery across the blood–brain barrier · 2025
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• Cell membrane-coated nanoparticles: An emerging antibacterial platform for pathogens of food animals · 2023
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