Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review article
  • Published:

Targeting drugs to tumours using cell membrane-coated nanoparticles

Abstract

Traditional cancer therapeutics, such as chemotherapies, are often limited by their non-specific nature, causing harm to non-malignant tissues. Over the past several decades, nanomedicine researchers have sought to address this challenge by developing nanoscale platforms capable of more precisely delivering drug payloads. Cell membrane-coated nanoparticles (CNPs) are an emerging class of nanocarriers that have demonstrated considerable promise for biomedical applications. Consisting of a synthetic nanoparticulate core camouflaged by a layer of naturally derived cell membranes, CNPs are adept at operating within complex biological environments; depending on the type of cell membrane utilized, the resulting biomimetic nanoformulation is conferred with several properties typically associated with the source cell, including improved biocompatibility, immune evasion and tumour targeting. In comparison with traditional functionalization approaches, cell membrane coating provides a streamlined method for creating multifunctional and multi-antigenic nanoparticles. In this Review, we discuss the history and development of CNPs as well as how these platforms have been used for cancer therapy. The application of CNPs for drug delivery, phototherapy and immunotherapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CNPs.

Key points

  • Cell membrane-coated nanoparticles (CNPs) are an emerging class of nanocarriers that are inherently multifunctional, combining the properties of synthetic nanoparticle cores with the bio-interfacing properties of cell membranes.

  • The type of membrane that is utilized is usually reflected in the biological properties of the resulting CNP, which can be further fine-tuned or augmented using various engineering approaches.

  • CNP technology has the potential to be applied in several therapeutic areas of oncology, including drug delivery, phototherapy and immunotherapy.

  • Efforts to translate promising CNPs into approved therapies are currently under way and will require the development of large-scale production methods and novel assays to facilitate the clinical adoption of CNPs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Traditional synthetic nanocarriers versus cell membrane-coated nanoparticles.
Fig. 2: Fabrication of cell membrane-coated nanoparticles.
Fig. 3: Common membrane sources for the fabrication of cell membrane-coated nanoparticles.
Fig. 4: Approaches for cell membrane modification.
Fig. 5: Anticancer applications of cell membrane-coated nanoparticles.

Similar content being viewed by others

References

  1. Gangadhar, T. C. & Vonderheide, R. H. Mitigating the toxic effects of anticancer immunotherapy. Nat. Rev. Clin. Oncol. 11, 91–99 (2014).

    Article  CAS  Google Scholar 

  2. Bower, J. E. Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat. Rev. Clin. Oncol. 11, 597–609 (2014).

    Article  CAS  Google Scholar 

  3. Stone, J. B. & DeAngelis, L. M. Cancer-treatment-induced neurotoxicity — focus on newer treatments. Nat. Rev. Clin. Oncol. 13, 92–105 (2016).

    Article  CAS  Google Scholar 

  4. Holohan, C., Van Schaeybroeck, S., Longley, D. B. & Johnston, P. G. Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer 13, 714–726 (2013).

    Article  CAS  Google Scholar 

  5. Vasan, N., Baselga, J. & Hyman, D. M. A view on drug resistance in cancer. Nature 575, 299–309 (2019).

    Article  CAS  Google Scholar 

  6. Drago, J. Z., Modi, S. & Chandarlapaty, S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat. Rev. Clin. Oncol. 18, 327–344 (2021).

    Article  Google Scholar 

  7. Llovet, J. M., Montal, R., Sia, D. & Finn, R. S. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 15, 599–616 (2018).

    Article  Google Scholar 

  8. Davis, M. E., Chen, Z. G. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7, 771–782 (2008).

    Article  CAS  Google Scholar 

  9. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1, 16014 (2016).

    Article  CAS  Google Scholar 

  10. Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007).

    Article  CAS  Google Scholar 

  11. Rosenblum, D., Joshi, N., Tao, W., Karp, J. M. & Peer, D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun. 9, 1410 (2018).

    Article  Google Scholar 

  12. Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101–124 (2021).

    Article  CAS  Google Scholar 

  13. Patra, J. K. et al. Nano based drug delivery systems: recent developments and future prospects. J. Nanobiotechnol. 16, 71 (2018).

    Article  Google Scholar 

  14. Barenholz, Y. Doxil® — the first FDA-approved nano-drug: lessons learned. J. Control. Rel. 160, 117–134 (2012).

    Article  CAS  Google Scholar 

  15. Yardley, D. A. nab-Paclitaxel mechanisms of action and delivery. J. Control. Rel. 170, 365–372 (2013).

    Article  CAS  Google Scholar 

  16. Lancet, J. E. et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J. Clin. Oncol. 36, 2684–2692 (2018).

    Article  CAS  Google Scholar 

  17. Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).

    Article  CAS  Google Scholar 

  18. Suk, J. S., Xu, Q. G., Kim, N., Hanes, J. & Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 99, 28–51 (2016).

    Article  CAS  Google Scholar 

  19. Abu Lila, A. S., Kiwada, H. & Ishida, T. The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. J. Control. Rel. 172, 38–47 (2013).

    Article  CAS  Google Scholar 

  20. Torchilin, V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv. Drug Deliv. Rev. 63, 131–135 (2011).

    Article  CAS  Google Scholar 

  21. Wu, C. H., Liu, I. J., Lu, R. M. & Wu, H. C. Advancement and applications of peptide phage display technology in biomedical science. J. Biomed. Sci. 23, 8 (2016).

    Article  Google Scholar 

  22. Little, M., Kipriyanov, S. M., Le Gall, F. & Moldenhauer, G. Of mice and men: hybridoma and recombinant antibodies. Immunol. Today 21, 364–370 (2000).

    Article  CAS  Google Scholar 

  23. Darmostuk, M., Rimpelova, S., Gbelcova, H. & Ruml, T. Current approaches in SELEX: an update to aptamer selection technology. Biotechnol. Adv. 33, 1141–1161 (2015).

    Article  CAS  Google Scholar 

  24. Yoo, J. W., Irvine, D. J., Discher, D. E. & Mitragotri, S. Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat. Rev. Drug Discov. 10, 521–535 (2011).

    Article  CAS  Google Scholar 

  25. Fang, R. H., Kroll, A. V., Gao, W. & Zhang, L. Cell membrane coating nanotechnology. Adv. Mater. 30, 1706759 (2018).

    Article  Google Scholar 

  26. Fang, R. H., Jiang, Y., Fang, J. C. & Zhang, L. Cell membrane-derived nanomaterials for biomedical applications. Biomaterials 128, 69–83 (2017).

    Article  CAS  Google Scholar 

  27. Molinaro, R. et al. Biomimetic proteolipid vesicles for targeting inflamed tissues. Nat. Mater. 15, 1037–1046 (2016).

    Article  CAS  Google Scholar 

  28. Toledano Furman, N. E. et al. Reconstructed stem cell nanoghosts: a natural tumor targeting platform. Nano Lett. 13, 3248–3255 (2013).

    Article  CAS  Google Scholar 

  29. Jiang, Y., Chekuri, S., Fang, R. H. & Zhang, L. Engineering biological interactions on the nanoscale. Curr. Opin. Biotechnol. 58, 1–8 (2019).

    Article  CAS  Google Scholar 

  30. Krishnan, N., Fang, R. H. & Zhang, L. Engineering of stimuli-responsive self-assembled biomimetic nanoparticles. Adv. Drug Deliv. Rev. 179, 114006 (2021).

    Article  CAS  Google Scholar 

  31. Oldenborg, P. A. et al. Role of CD47 as a marker of self on red blood cells. Science 288, 2051–2054 (2000).

    Article  CAS  Google Scholar 

  32. Hu, C.-M. J. et al. ‘Marker-of-self’ functionalization of nanoscale particles through a top-down cellular membrane coating approach. Nanoscale 5, 2664–2668 (2013).

    Article  CAS  Google Scholar 

  33. Fang, R. H. et al. Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug delivery. Nano Lett. 14, 2181–2188 (2014).

    Article  CAS  Google Scholar 

  34. Hu, C. M. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).

    Article  CAS  Google Scholar 

  35. Zhou, J. et al. Physical disruption of solid tumors by immunostimulatory microrobots enhances antitumor immunity. Adv. Mater. 33, 2103505 (2021).

    Article  CAS  Google Scholar 

  36. Jiang, Y. et al. Engineered cell-membrane-coated nanoparticles directly present tumor antigens to promote anticancer immunity. Adv. Mater. 32, 2001808 (2020).

    Article  CAS  Google Scholar 

  37. Hu, C. M. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980–10985 (2011).

    Article  CAS  Google Scholar 

  38. Noris, M. & Remuzzi, G. Overview of complement activation and regulation. Semin. Nephrol. 33, 479–492 (2013).

    Article  CAS  Google Scholar 

  39. Fang, R. H., Hu, C. M. J. & Zhang, L. F. Nanoparticles disguised as red blood cells to evade the immune system. Expert Opin. Biol. Ther. 12, 385–389 (2012).

    Article  CAS  Google Scholar 

  40. Rao, L. et al. Red blood cell membrane as a biomimetic nanocoating for prolonged circulation time and reduced accelerated blood clearance. Small 11, 6225–6236 (2015).

    Article  CAS  Google Scholar 

  41. Olsson, M., Bruhns, P., Frazier, W. A., Ravetch, J. V. & Oldenborg, P. A. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia. Blood 105, 3577–3582 (2005).

    Article  CAS  Google Scholar 

  42. Gay, L. J. & Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nat. Rev. Cancer 11, 123–134 (2011).

    Article  CAS  Google Scholar 

  43. Schlesinger, M. Role of platelets and platelet receptors in cancer metastasis. J. Hematol. Oncol. 11, 125 (2018).

    Article  CAS  Google Scholar 

  44. Zamarron, B. F. & Chen, W. J. Dual roles of immune cells and their factors in cancer development and progression. Int. J. Biol. Sci. 7, 651–658 (2011).

    Article  CAS  Google Scholar 

  45. Gonzalez, H., Hagerling, C. & Werb, Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 32, 1267–1284 (2018).

    Article  CAS  Google Scholar 

  46. Harris, J. C., Scully, M. A. & Day, E. S. Cancer cell membrane-coated nanoparticles for cancer management. Cancers 11, 1836 (2019).

    Article  CAS  Google Scholar 

  47. Rao, L. et al. Cancer cell membrane-coated upconversion nanoprobes for highly specific tumor imaging. Adv. Mater. 28, 3460–3466 (2016).

    Article  CAS  Google Scholar 

  48. Glinsky, V. V. et al. Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Cancer Res. 63, 3805–3811 (2003).

    CAS  Google Scholar 

  49. Kroll, A. V. et al. Nanoparticulate delivery of cancer cell membrane elicits multiantigenic antitumor immunity. Adv. Mater. 29, 1703969 (2017).

    Article  Google Scholar 

  50. Ye, X. et al. Surgical tumor-derived personalized photothermal vaccine formulation for cancer immunotherapy. ACS Nano 13, 2956–2968 (2019).

    Article  CAS  Google Scholar 

  51. Wang, M. et al. Recent advances in mesenchymal stem cell membrane-coated nanoparticles for enhanced drug delivery. Biomater. Sci. 9, 1088–1103 (2021).

    Article  CAS  Google Scholar 

  52. Zhang, W. & Huang, X. Stem cell membrane-camouflaged targeted delivery system in tumor. Mater. Today Bio 16, 100377 (2022).

    Article  CAS  Google Scholar 

  53. Li, J. et al. Cell membrane coated semiconducting polymer nanoparticles for enhanced multimodal cancer phototheranostics. ACS Nano 12, 8520–8530 (2018).

    Article  CAS  Google Scholar 

  54. Krishnan, N. et al. Bacterial membrane vesicles for vaccine applications. Adv. Drug Deliv. Rev. 185, 114294 (2022).

    Article  CAS  Google Scholar 

  55. Gao, W. W. et al. Modulating antibacterial immunity via bacterial membrane-coated nanoparticles. Nano Lett. 15, 1403–1409 (2015).

    Article  CAS  Google Scholar 

  56. Mogensen, T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 22, 240–273 (2009).

    Article  CAS  Google Scholar 

  57. Zemek, R. M. et al. Sensitizing the tumor microenvironment to immune checkpoint therapy. Front. Immunol. 11, 223 (2020).

    Article  CAS  Google Scholar 

  58. Drake, C. G. Combination immunotherapy approaches. Ann. Oncol. 23, viii41–viii46 (2012).

    Article  Google Scholar 

  59. McCarthy, E. F. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop. J. 26, 154–158 (2006).

    Google Scholar 

  60. Holay, M. et al. Bacteria-inspired nanomedicine. ACS Appl. Bio Mater. 4, 3830–3848 (2021).

    Article  CAS  Google Scholar 

  61. Zariri, A. et al. Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response. Infect. Immun. 84, 3024–3033 (2016).

    Article  CAS  Google Scholar 

  62. Moore, G. E. & Ulrich, K. Suspension cultures of mammalian cells: a review. J. Surg. Res. 5, 270–282 (1965).

    Article  CAS  Google Scholar 

  63. Baek, E. J. et al. In vitro clinical-grade generation of red blood cells from human umbilical cord blood CD34+ cells. Transfusion 48, 2235–2245 (2008).

    Article  Google Scholar 

  64. Ito, Y. et al. Turbulence activates platelet biogenesis to enable clinical scale ex vivo production. Cell 174, 636–648.e18 (2018).

    Article  CAS  Google Scholar 

  65. van Niel, G., D’Angelo, G. & Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19, 213–228 (2018).

    Article  Google Scholar 

  66. Holay, M. et al. Organotropic targeting of biomimetic nanoparticles to treat lung disease. Bioconjug. Chem. 33, 586–593 (2022).

    Article  CAS  Google Scholar 

  67. Copp, J. A. et al. Clearance of pathological antibodies using biomimetic nanoparticles. Proc. Natl Acad. Sci. USA 111, 13481–13486 (2014).

    Article  CAS  Google Scholar 

  68. Rao, L. et al. Microfluidic electroporation-facilitated synthesis of erythrocyte membrane-coated magnetic nanoparticles for enhanced imaging-guided cancer therapy. ACS Nano 11, 3496–3505 (2017).

    Article  CAS  Google Scholar 

  69. Sherwood, J. et al. Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices. Nanoscale 11, 6352–6359 (2019).

    Article  CAS  Google Scholar 

  70. Luk, B. T. et al. Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles. Nanoscale 6, 2730–2737 (2014).

    Article  CAS  Google Scholar 

  71. Gao, W. et al. Surface functionalization of gold nanoparticles with red blood cell membranes. Adv. Mater. 25, 3549–3553 (2013).

    Article  CAS  Google Scholar 

  72. Fang, R. H. et al. Lipid-insertion enables targeting functionalization of erythrocyte membrane-cloaked nanoparticles. Nanoscale 5, 8884–8888 (2013).

    Article  CAS  Google Scholar 

  73. Dehaini, D. et al. Erythrocyte–platelet hybrid membrane coating for enhanced nanoparticle functionalization. Adv. Mater. 29, 1606209 (2017).

    Article  Google Scholar 

  74. Park, J. H. et al. Genetically engineered cell membrane-coated nanoparticles for targeted delivery of dexamethasone to inflamed lungs. Sci. Adv. 7, eabf7820 (2021).

    Article  CAS  Google Scholar 

  75. Park, J. H. et al. Virus-mimicking cell membrane-coated nanoparticles for cytosolic delivery of mRNA. Angew. Chem. Int. Ed. Engl. 61, e202113671 (2022).

    Article  CAS  Google Scholar 

  76. Ai, X. et al. Surface glycan modification of cellular nanosponges to promote SARS-CoV-2 inhibition. J. Am. Chem. Soc. 143, 17615–17621 (2021).

    Article  CAS  Google Scholar 

  77. Aryal, S. et al. Erythrocyte membrane-cloaked polymeric nanoparticles for controlled drug loading and release. Nanomedicine 8, 1271–1280 (2013).

    Article  CAS  Google Scholar 

  78. Fu, Q. et al. Programmed co-delivery of paclitaxel and doxorubicin boosted by camouflaging with erythrocyte membrane. Nanoscale 7, 4020–4030 (2015).

    Article  CAS  Google Scholar 

  79. Luk, B. T. et al. Safe and immunocompatible nanocarriers cloaked in RBC membranes for drug delivery to treat solid tumors. Theranostics 6, 1004–1011 (2016).

    Article  CAS  Google Scholar 

  80. Su, J. et al. Enhanced blood suspensibility and laser-activated tumor-specific drug release of theranostic mesoporous silica nanoparticles by functionalizing with erythrocyte membranes. Theranostics 7, 523–537 (2017).

    Article  CAS  Google Scholar 

  81. Zhang, L. et al. Erythrocyte membrane cloaked metal–organic framework nanoparticle as biomimetic nanoreactor for starvation-activated colon cancer therapy. ACS Nano 12, 10201–10211 (2018).

    Article  CAS  Google Scholar 

  82. Zhuang, J. et al. Targeted gene silencing in vivo by platelet membrane–coated metal-organic framework nanoparticles. Sci. Adv. 6, eaaz6108 (2020).

    Article  CAS  Google Scholar 

  83. Zhang, Y. et al. Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection. J. Control. Rel. 263, 185–191 (2017).

    Article  CAS  Google Scholar 

  84. Gao, C. et al. Stem cell membrane-coated nanogels for highly efficient in vivo tumor targeted drug delivery. Small 12, 4056–4062 (2016).

    Article  CAS  Google Scholar 

  85. Zhang, X. et al. Remote loading of small-molecule therapeutics into cholesterol-enriched cell-membrane-derived vesicles. Angew. Chem. Int. Ed. Engl. 56, 14075–14079 (2017).

    Article  CAS  Google Scholar 

  86. Zou, M. Z. et al. Artificial natural killer cells for specific tumor inhibition and renegade macrophage re-education. Adv. Mater. 31, 1904495 (2019).

    Article  CAS  Google Scholar 

  87. Zhuang, J. et al. Biomimetic nanoemulsions for oxygen delivery in vivo. Adv. Mater. 30, 1804693 (2018).

    Article  Google Scholar 

  88. Miao, Y. et al. Cell membrane-camouflaged nanocarriers with biomimetic deformability of erythrocytes for ultralong circulation and enhanced cancer therapy. ACS Nano 16, 6527–6540 (2022).

    Article  CAS  Google Scholar 

  89. Zou, Y. et al. Effective and targeted human orthotopic glioblastoma xenograft therapy via a multifunctional biomimetic nanomedicine. Adv. Mater. 30, 1803717 (2018).

    Article  Google Scholar 

  90. Chai, Z. et al. Ligand-modified cell membrane enables the targeted delivery of drug nanocrystals to glioma. ACS Nano 13, 5591–5601 (2019).

    Article  CAS  Google Scholar 

  91. Zhai, Y. et al. Traceable bioinspired nanoparticle for the treatment of metastatic breast cancer via NIR-trigged intracellular delivery of methylene blue and cisplatin. Adv. Mater. 30, 1802378 (2018).

    Article  Google Scholar 

  92. Sung, S. Y. et al. Graphene quantum dots-mediated theranostic penetrative delivery of drug and photolytics in deep tumors by targeted biomimetic nanosponges. Nano Lett. 19, 69–81 (2019).

    Article  CAS  Google Scholar 

  93. Gao, L. et al. Erythrocyte membrane-wrapped pH sensitive polymeric nanoparticles for non-small cell lung cancer therapy. Bioconjug. Chem. 28, 2591–2598 (2017).

    Article  CAS  Google Scholar 

  94. Song, Q. et al. Tumor microenvironment responsive nanogel for the combinatorial antitumor effect of chemotherapy and immunotherapy. Nano Lett. 17, 6366–6375 (2017).

    Article  CAS  Google Scholar 

  95. Hu, Q. et al. Anticancer platelet-mimicking nanovehicles. Adv. Mater. 27, 7043–7050 (2015).

    Article  CAS  Google Scholar 

  96. Li, J. et al. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles. Biomaterials 76, 52–65 (2016).

    Article  CAS  Google Scholar 

  97. Hu, Q. et al. Engineered nanoplatelets for enhanced treatment of multiple myeloma and thrombus. Adv. Mater. 28, 9573–9580 (2016).

    Article  CAS  Google Scholar 

  98. Zhang, M. et al. Platelet-mimicking biotaxis targeting vasculature-disrupted tumors for cascade amplification of hypoxia-sensitive therapy. ACS Nano 13, 14230–14240 (2019).

    Article  CAS  Google Scholar 

  99. Ying, M. et al. Remote-loaded platelet vesicles for disease-targeted delivery of therapeutics. Adv. Funct. Mater. 28, 1801032 (2018).

    Article  Google Scholar 

  100. Cao, H. Q. et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer. ACS Nano 10, 7738–7748 (2016).

    Article  CAS  Google Scholar 

  101. Zhang, Y. et al. Macrophage-membrane-coated nanoparticles for tumor-targeted chemotherapy. Nano Lett. 18, 1908–1915 (2018).

    Article  CAS  Google Scholar 

  102. Kang, T. et al. Nanoparticles coated with neutrophil membranes can effectively treat cancer metastasis. ACS Nano 11, 1397–1411 (2017).

    Article  CAS  Google Scholar 

  103. Zhang, C. et al. Artificial super neutrophils for inflammation targeting and HClO generation against tumors and infections. Adv. Mater. 31, 1901179 (2019).

    Article  Google Scholar 

  104. Sun, H. et al. Cancer-cell-biomimetic nanoparticles for targeted therapy of homotypic tumors. Adv. Mater. 28, 9581–9588 (2016).

    Article  CAS  Google Scholar 

  105. Zhu, J. Y. et al. Preferential cancer cell self-recognition and tumor self-targeting by coating nanoparticles with homotypic cancer cell membranes. Nano Lett. 16, 5895–5901 (2016).

    Article  CAS  Google Scholar 

  106. Shao, D. et al. Bioinspired diselenide-bridged mesoporous silica nanoparticles for dual-responsive protein delivery. Adv. Mater. 30, 1801198 (2018).

    Article  Google Scholar 

  107. Shao, D. et al. Biomimetic diselenide-bridged mesoporous organosilica nanoparticles as an X-ray-responsive biodegradable carrier for chemo-immunotherapy. Adv. Mater. 32, 2004385 (2020).

    Article  CAS  Google Scholar 

  108. Bose, R. J. C. et al. Tumor cell-derived extracellular vesicle-coated nanocarriers: an efficient theranostic platform for the cancer-specific delivery of anti-miR-21 and imaging agents. ACS Nano 12, 10817–10832 (2018).

    Article  Google Scholar 

  109. Xie, W. et al. Cancer cell membrane camouflaged nanoparticles to realize starvation therapy together with checkpoint blockades for enhancing cancer therapy. ACS Nano 13, 2849–2857 (2019).

    Article  CAS  Google Scholar 

  110. Chitgupi, U., Qin, Y. & Lovell, J. F. Targeted nanomaterials for phototherapy. Nanotheranostics 1, 38–58 (2017).

    Article  Google Scholar 

  111. Li, X., Lovell, J. F., Yoon, J. & Chen, X. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol. 17, 657–674 (2020).

    Article  Google Scholar 

  112. Piao, J. G. et al. Erythrocyte membrane is an alternative coating to polyethylene glycol for prolonging the circulation lifetime of gold nanocages for photothermal therapy. ACS Nano 8, 10414–10425 (2014).

    Article  CAS  Google Scholar 

  113. Ren, X. et al. Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy. Biomaterials 92, 13–24 (2016).

    Article  CAS  Google Scholar 

  114. Liu, Z. et al. Fabrication of red blood cell membrane-camouflaged Cu2-xSe nanoparticles for phototherapy in the second near-infrared window. Chem. Commun. 55, 6523–6526 (2019).

    Article  CAS  Google Scholar 

  115. Rao, L. et al. Antitumor platelet-mimicking magnetic nanoparticles. Adv. Funct. Mater. 27, 1604774 (2017).

    Article  Google Scholar 

  116. Chen, Z. et al. Cancer cell membrane-biomimetic nanoparticles for homologous-targeting dual-modal imaging and photothermal therapy. ACS Nano 10, 10049–10057 (2016).

    Article  CAS  Google Scholar 

  117. Han, Y. et al. T cell membrane mimicking nanoparticles with bioorthogonal targeting and immune recognition for enhanced photothermal therapy. Adv. Sci. 6, 1900251 (2019).

    Article  Google Scholar 

  118. Wang, D. et al. Erythrocyte–cancer hybrid membrane camouflaged hollow copper sulfide nanoparticles for prolonged circulation life and homotypic-targeting photothermal/chemotherapy of melanoma. ACS Nano 12, 5241–5252 (2018).

    Article  CAS  Google Scholar 

  119. Gao, C. et al. In vivo hitchhiking of immune cells by intracellular self-assembly of bacteria-mimetic nanomedicine for targeted therapy of melanoma. Sci. Adv. 8, eabn1805 (2022).

    Article  CAS  Google Scholar 

  120. Li, S. Y. et al. Cancer cell membrane camouflaged cascade bioreactor for cancer targeted starvation and photodynamic therapy. ACS Nano 11, 7006–7018 (2017).

    Article  CAS  Google Scholar 

  121. Yang, X. et al. Biomimetic hybrid nanozymes with self-supplied H+ and accelerated O2 generation for enhanced starvation and photodynamic therapy against hypoxic tumors. Nano Lett. 19, 4334–4342 (2019).

    Article  CAS  Google Scholar 

  122. Wang, J. P. et al. A porous Au@Rh bimetallic core–shell nanostructure as an H2O2-driven oxygenerator to alleviate tumor hypoxia for simultaneous bimodal imaging and enhanced photodynamic therapy. Adv. Mater. 32, 2001862 (2020).

    Article  CAS  Google Scholar 

  123. Liu, C. et al. Biodegradable biomimic copper/manganese silicate nanospheres for chemodynamic/photodynamic synergistic therapy with simultaneous glutathione depletion and hypoxia relief. ACS Nano 13, 4267–4277 (2019).

    Article  CAS  Google Scholar 

  124. Wang, Z. et al. Janus nanobullets combine photodynamic therapy and magnetic hyperthermia to potentiate synergetic anti-metastatic immunotherapy. Adv. Sci. 6, 1901690 (2019).

    Article  CAS  Google Scholar 

  125. Min, H. et al. Biomimetic metal–organic framework nanoparticles for cooperative combination of antiangiogenesis and photodynamic therapy for enhanced efficacy. Adv. Mater. 31, 1808200 (2019).

    Article  Google Scholar 

  126. Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018).

    Article  CAS  Google Scholar 

  127. Esfahani, K. et al. A review of cancer immunotherapy: from the past, to the present, to the future. Curr. Oncol. 27, S87–S97 (2020).

    Article  CAS  Google Scholar 

  128. Zhang, F. et al. Engineering magnetosomes for ferroptosis/immunomodulation synergism in cancer. ACS Nano 13, 5662–5673 (2019).

    Article  CAS  Google Scholar 

  129. Deng, G. et al. Cell-membrane immunotherapy based on natural killer cell membrane coated nanoparticles for the effective inhibition of primary and abscopal tumor growth. ACS Nano 12, 12096–12108 (2018).

    Article  CAS  Google Scholar 

  130. Zhang, J. et al. Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection. Nat. Nanotechnol. 16, 538–548 (2021).

    Article  CAS  Google Scholar 

  131. Rao, L. et al. Activating macrophage-mediated cancer immunotherapy by genetically edited nanoparticles. Adv. Mater. 32, 2004853 (2020).

    Article  CAS  Google Scholar 

  132. Zhang, X. et al. PD-1 blockade cellular vesicles for cancer immunotherapy. Adv. Mater. 30, 1707112 (2018).

    Article  Google Scholar 

  133. Zhai, Y. et al. T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy. Nat. Nanotechnol. 16, 1271–1280 (2021).

    Article  CAS  Google Scholar 

  134. Zhang, Y., Liao, Y., Tang, Q., Lin, J. & Huang, P. Biomimetic nanoemulsion for synergistic photodynamic-immunotherapy against hypoxic breast tumor. Angew. Chem. Int. Ed. Engl. 60, 10647–10653 (2021).

    Article  CAS  Google Scholar 

  135. Bahmani, B. et al. Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors. Nat. Commun. 12, 1999 (2021).

    Article  CAS  Google Scholar 

  136. Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2021).

    Article  CAS  Google Scholar 

  137. Higano, C. S. et al. Sipuleucel-T. Nat. Rev. Drug Discov. 9, 513–514 (2010).

    Article  CAS  Google Scholar 

  138. van der Burg, S. H., Arens, R., Ossendorp, F., van Hall, T. & Melief, C. J. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 16, 219–233 (2016).

    Article  Google Scholar 

  139. Zhou, J., Kroll, A. V., Holay, M., Fang, R. H. & Zhang, L. Biomimetic nanotechnology toward personalized vaccines. Adv. Mater. 32, 1901255 (2020).

    Article  CAS  Google Scholar 

  140. Guo, Y. Y. et al. Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma. ACS Nano 9, 6918–6933 (2015).

    Article  CAS  Google Scholar 

  141. Reuven, E. M. et al. Biomimetic glyconanoparticle vaccine for cancer immunotherapy. ACS Nano 13, 2936–2947 (2019).

    Article  CAS  Google Scholar 

  142. Fontana, F. et al. Multistaged nanovaccines based on porous silicon@acetalated dextran@cancer cell membrane for cancer immunotherapy. Adv. Mater. 29, 1603239 (2017).

    Article  Google Scholar 

  143. Yang, R. et al. Cancer cell membrane-coated adjuvant nanoparticles with mannose modification for effective anticancer vaccination. ACS Nano 12, 5121–5129 (2018).

    Article  CAS  Google Scholar 

  144. Chen, Q. et al. A hybrid eukaryotic-prokaryotic nanoplatform with photothermal modality for enhanced antitumor vaccination. Adv. Mater. 32, 1908185 (2020).

    Article  CAS  Google Scholar 

  145. Zhai, Y. W. et al. A splenic-targeted versatile antigen courier: iPSC wrapped in coalescent erythrocyte-liposome as tumor nanovaccine. Sci. Adv. 7, eabi6326 (2021).

    Article  CAS  Google Scholar 

  146. Hammerich, L., Binder, A. & Brody, J. D. In situ vaccination: cancer immunotherapy both personalized and off-the-shelf. Mol. Oncol. 9, 1966–1981 (2015).

    Article  CAS  Google Scholar 

  147. Patel, R. B. et al. Development of an in situ cancer vaccine via combinational radiation and bacterial-membrane-coated nanoparticles. Adv. Mater. 31, 1902626 (2019).

    Article  CAS  Google Scholar 

  148. Eggermont, L. J., Paulis, L. E., Tel, J. & Figdor, C. G. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells. Trends Biotechnol. 32, 456–465 (2014).

    Article  CAS  Google Scholar 

  149. Zhang, Q. B. et al. Biomimetic magnetosomes as versatile artificial antigen-presenting cells to potentiate T-cell-based anticancer therapy. ACS Nano 11, 10724–10732 (2017).

    Article  CAS  Google Scholar 

  150. Liu, W. L. et al. Expandable immunotherapeutic nanoplatforms engineered from cytomembranes of hybrid cells derived from cancer and dendritic cells. Adv. Mater. 31, 1900499 (2019).

    Article  Google Scholar 

  151. Xiao, P. et al. Engineering nanoscale artificial antigen-presenting cells by metabolic dendritic cell labeling to potentiate cancer immunotherapy. Nano Lett. 21, 2094–2103 (2021).

    Article  CAS  Google Scholar 

  152. Herrmann, I. K., Wood, M. J. A. & Fuhrmann, G. Extracellular vesicles as a next-generation drug delivery platform. Nat. Nanotechnol. 16, 748–759 (2021).

    Article  CAS  Google Scholar 

  153. Anselmo, A. C. & Mitragotri, S. Nanoparticles in the clinic: an update. Bioeng. Transl. Med. 4, e10143 (2019).

    Article  Google Scholar 

  154. Busatto, S. et al. Tangential flow filtration for highly efficient concentration of extracellular vesicles from large volumes of fluid. Cells 7, 273 (2018).

    Article  CAS  Google Scholar 

  155. Ganesan, P., Karthivashan, G., Park, S. Y., Kim, J. & Choi, D. K. Microfluidization trends in the development of nanodelivery systems and applications in chronic disease treatments. Int. J. Nanomed. 13, 6109–6121 (2018).

    Article  CAS  Google Scholar 

  156. Wortzel, I., Dror, S., Kenific, C. M. & Lyden, D. Exosome-mediated metastasis: communication from a distance. Dev. Cell 49, 347–360 (2019).

    Article  CAS  Google Scholar 

  157. Jensen, C. & Teng, Y. Is it time to start transitioning from 2D to 3D cell culture? Front. Mol. Biosci. 7, 33 (2020).

    Article  CAS  Google Scholar 

  158. Szczepiorkowski, Z. M. & Dunbar, N. M. Transfusion guidelines: when to transfuse. Hematol. Am. Soc. Hematol. Educ. Program 2013, 638–644 (2013).

    Article  Google Scholar 

  159. Shlomchik, W. D. Graft-versus-host disease. Nat. Rev. Immunol. 7, 340–352 (2007).

    Article  CAS  Google Scholar 

  160. Ren, J. et al. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clin. Cancer Res. 23, 2255–2266 (2017).

    Article  CAS  Google Scholar 

  161. Gornalusse, G. G. et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 35, 765–772 (2017).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The work of the authors is supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under Grant Number HDTRA1‐21‐1‐0010, the National Institutes of Health under Award Number R01CA200574 and the National Science Foundation Grant DMR-1904702.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to all aspects of the preparation of this manuscript prior to submission.

Corresponding author

Correspondence to Liangfang Zhang.

Ethics declarations

Competing interests

L.Z. is the founder of Cellics Therapeutics and Cello Therapeutics and holds equity interests in both companies. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Clinical Oncology thanks X. Chen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fang, R.H., Gao, W. & Zhang, L. Targeting drugs to tumours using cell membrane-coated nanoparticles. Nat Rev Clin Oncol 20, 33–48 (2023). https://doi.org/10.1038/s41571-022-00699-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41571-022-00699-x

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research