Cell membrane-coated nanoparticles for cancer therapy


  • Yasir Hameed Department of Applied Biological Sciences, Tokyo University of Science, Tokyo, Japan
  • Mohsen Nabi-Afjadi Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran https://orcid.org/0000-0001-8243-1530
  • Yuan Gu The Statistics Department, The George Washington University, Washington, United States https://orcid.org/0000-0001-6222-7241
  • Long Wu Department of Surgery, University of Maryland, Baltimore, United States




Cell membrane; Nanoparticles; Drug delivery; Cancer


Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.


Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660

Saez-Rodriguez J, MacNamara A, Cook S. Modeling Signaling Networks to Advance New Cancer Therapies. Annu Rev Biomed Eng. 2015;17:143-163. doi:10.1146/annurev-bioeng-071813-104927

Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer. 2012;12(5):323-334. doi:10.1038/nrc3261

Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941-951. doi:10.1038/nbt.3330

Wilhelm S, Tavares AJ, Dai Q, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016;1(5):1-12. doi:10.1038/natrevmats.2016.14

Kobsa S, Saltzman WM. Bioengineering Approaches to Controlled Protein Delivery. Pediatr Res. 2008;63(5):513-519. doi:10.1203/PDR.0b013e318165f14d

Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med. 2012;63:185-198. doi:10.1146/annurev-med-040210-162544

Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. The golden age: gold nanoparticles for biomedicine. Chem Soc Rev. 2012;41(7):2740-2779. doi:10.1039/c1cs15237h

Xie J, Lee S, Chen X. Nanoparticle-based theranostic agents. Adv Drug Deliv Rev. 2010;62(11):1064-1079. doi:10.1016/j.addr.2010.07.009

Kievit FM, Zhang M. Cancer nanotheranostics: improving imaging and therapy by targeted delivery across biological barriers. Adv Mater Deerfield Beach Fla. 2011;23(36):H217-247. doi:10.1002/adma.201102313

Rizzo LY, Theek B, Storm G, Kiessling F, Lammers T. Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications. Curr Opin Biotechnol. 2013;24(6):1159-1166. doi:10.1016/j.copbio.2013.02.020

Tassa C, Shaw SY, Weissleder R. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. Acc Chem Res. 2011;44(10):842-852. doi:10.1021/ar200084x

Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990;268(1):235-237. doi:10.1016/0014-5793(90)81016-h

Lee DE, Koo H, Sun IC, Ryu JH, Kim K, Kwon IC. Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem Soc Rev. 2012;41(7):2656-2672. doi:10.1039/c2cs15261d

Cheng L, Wang C, Feng L, Yang K, Liu Z. Functional nanomaterials for phototherapies of cancer. Chem Rev. 2014;114(21):10869-10939. doi:10.1021/cr400532z

Kim DH, Vitol EA, Liu J, et al. Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles. Langmuir ACS J Surf Colloids. 2013;29(24):7425-7432. doi:10.1021/la3044158

Chen H, Zhang W, Zhu G, Xie J, Chen X. Rethinking cancer nanotheranostics. Nat Rev Mater. 2017;2:17024. doi:10.1038/natrevmats.2017.24

Lammers T, Kiessling F, Ashford M, Hennink W, Crommelin D, Storm G. Cancer nanomedicine: Is targeting our target? Nat Rev Mater. 2016;1(9):16069. doi:10.1038/natrevmats.2016.69

Yang Q, Lai SK. Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2015;7(5):655-677. doi:10.1002/wnan.1339

Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-160. doi:10.1038/nrd1632

Fang RH, Jiang Y, Fang JC, Zhang L. Cell membrane-derived nanomaterials for biomedical applications. Biomaterials. 2017;128:69-83. doi:10.1016/j.biomaterials.2017.02.041

Zhang L, Wu S, Qin Y, et al. Targeted Codelivery of an Antigen and Dual Agonists by Hybrid Nanoparticles for Enhanced Cancer Immunotherapy. Nano Lett. 2019;19(7):4237-4249. doi:10.1021/acs.nanolett.9b00030

Luk BT, Zhang L. Cell membrane-camouflaged nanoparticles for drug delivery. J Control Release Off J Control Release Soc. 2015;220(Pt B):600-607. doi:10.1016/j.jconrel.2015.07.019

Hu CMJ, Fang RH, Zhang L. Erythrocyte-inspired delivery systems. Adv Healthc Mater. 2012;1(5):537-547. doi:10.1002/adhm.201200138

Hu CMJ, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc Natl Acad Sci U S A. 2011;108(27):10980-10985. doi:10.1073/pnas.1106634108

Yang Z, Gao D, Guo X, et al. Fighting Immune Cold and Reprogramming Immunosuppressive Tumor Microenvironment with Red Blood Cell Membrane-Camouflaged Nanobullets. ACS Nano. 2020;14(12):17442-17457. doi:10.1021/acsnano.0c07721

Fang RH, Hu CMJ, Chen KNH, et al. Lipid-insertion enables targeting functionalization of erythrocyte membrane-cloaked nanoparticles. Nanoscale. 2013;5(19):8884-8888. doi:10.1039/c3nr03064d

Zhao H, Wu L, Yan G, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther. 2021;6(1):263. doi:10.1038/s41392-021-00658-5

Parodi A, Quattrocchi N, van de Ven AL, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol. 2013;8(1):61-68. doi:10.1038/nnano.2012.212

Molinaro R, Corbo C, Martinez JO, et al. Biomimetic proteolipid vesicles for targeting inflamed tissues. Nat Mater. 2016;15(9):1037-1046. doi:10.1038/nmat4644

Kang T, Zhu Q, Wei D, et al. Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis. ACS Nano. 2017;11(2):1397-1411. doi:10.1021/acsnano.6b06477

Meng Z, Zhang Y, Zhou X, Ji J, Liu Z. Nanovaccines with cell-derived components for cancer immunotherapy. Adv Drug Deliv Rev. 2022;182:114107. doi:10.1016/j.addr.2021.114107

Xue J, Zhao Z, Zhang L, et al. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nat Nanotechnol. 2017;12(7):692-700. doi:10.1038/nnano.2017.54

Zhang L, Li R, Chen H, et al. Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer. Int J Nanomedicine. 2017;12:2129-2142. doi:10.2147/IJN.S126016

Kallert SM, Darbre S, Bonilla WV, et al. Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy. Nat Commun. 2017;8:15327. doi:10.1038/ncomms15327

Deng G, Sun Z, Li S, 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. 2018;12(12):12096-12108. doi:10.1021/acsnano.8b05292

Harris JC, Scully MA, Day ES. Cancer Cell Membrane-Coated Nanoparticles for Cancer Management. Cancers. 2019;11(12):1836. doi:10.3390/cancers11121836

Liu X, Sun Y, Xu S, et al. Homotypic Cell Membrane-Cloaked Biomimetic Nanocarrier for the Targeted Chemotherapy of Hepatocellular Carcinoma. Theranostics. 2019;9(20):5828-5838. doi:10.7150/thno.34837

Liu CM, Chen GB, Chen HH, et al. Cancer cell membrane-cloaked mesoporous silica nanoparticles with a pH-sensitive gatekeeper for cancer treatment. Colloids Surf B Biointerfaces. 2019;175:477-486. doi:10.1016/j.colsurfb.2018.12.038

Wang H, Wang K, He L, Liu Y, Dong H, Li Y. Engineering antigen as photosensitiser nanocarrier to facilitate ROS triggered immune cascade for photodynamic immunotherapy. Biomaterials. 2020;244:119964. doi:10.1016/j.biomaterials.2020.119964

Kroll AV, Fang RH, Jiang Y, et al. Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity. Adv Mater Deerfield Beach Fla. 2017;29(47). doi:10.1002/adma.201703969

Dehaini D, Wei X, Fang RH, et al. Erythrocyte-Platelet Hybrid Membrane Coating for Enhanced Nanoparticle Functionalization. Adv Mater Deerfield Beach Fla. 2017;29(16). doi:10.1002/adma.201606209

Wang D, Dong H, Li M, et al. Erythrocyte-Cancer Hybrid Membrane Camouflaged Hollow Copper Sulfide Nanoparticles for Prolonged Circulation Life and Homotypic-Targeting Photothermal/Chemotherapy of Melanoma. ACS Nano. 2018;12(6):5241-5252. doi:10.1021/acsnano.7b08355

Chen HY, Deng J, Wang Y, Wu CQ, Li X, Dai HW. Hybrid cell membrane-coated nanoparticles: A multifunctional biomimetic platform for cancer diagnosis and therapy. Acta Biomater. 2020;112:1-13. doi:10.1016/j.actbio.2020.05.028

Wu HH, Zhou Y, Tabata Y, Gao JQ. Mesenchymal stem cell-based drug delivery strategy: from cells to biomimetic. J Control Release Off J Control Release Soc. 2019;294:102-113. doi:10.1016/j.jconrel.2018.12.019

Zhang M, Cheng S, Jin Y, Zhang N, Wang Y. Membrane engineering of cell membrane biomimetic nanoparticles for nanoscale therapeutics. Clin Transl Med. 2021;11(2):e292. doi:10.1002/ctm2.292

Mu X, Li J, Yan S, et al. siRNA Delivery with Stem Cell Membrane-Coated Magnetic Nanoparticles for Imaging-Guided Photothermal Therapy and Gene Therapy. ACS Biomater Sci Eng. 2018;4(11):3895-3905. doi:10.1021/acsbiomaterials.8b00858

Tran PHL, Xiang D, Tran TTD, et al. Exosomes and Nanoengineering: A Match Made for Precision Therapeutics. Adv Mater Deerfield Beach Fla. 2020;32(18):e1904040. doi:10.1002/adma.201904040

Yong T, Zhang X, Bie N, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat Commun. 2019;10(1):3838. doi:10.1038/s41467-019-11718-4

Ren X, Zheng R, Fang X, et al. Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy. Biomaterials. 2016;92:13-24. doi:10.1016/j.biomaterials.2016.03.026

Rao L, Xu JH, Cai B, et al. Synthetic nanoparticles camouflaged with biomimetic erythrocyte membranes for reduced reticuloendothelial system uptake. Nanotechnology. 2016;27(8):085106. doi:10.1088/0957-4484/27/8/085106

Rao L, Bu LL, Cai B, et al. Cancer Cell Membrane-Coated Upconversion Nanoprobes for Highly Specific Tumor Imaging. Adv Mater. 2016;28(18):3460-3466. doi:10.1002/adma.201506086

Chen Z, Zhao P, Luo Z, et al. Cancer Cell Membrane–Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy. ACS Nano. 2016;10(11):10049-10057. doi:10.1021/acsnano.6b04695

Chen X, Lee D, Yu S, et al. In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe. Biomaterials. 2017;122:130-140. doi:10.1016/j.biomaterials.2017.01.020

Vijayan V, Uthaman S, Park IK. Cell Membrane-Camouflaged Nanoparticles: A Promising Biomimetic Strategy for Cancer Theragnostics. Polymers. 2018;10(9):983. doi:10.3390/polym10090983

Meng QF, Rao L, Zan M, et al. Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal tumor therapy. Nanotechnology. 2018;29(13):134004. doi:10.1088/1361-6528/aaa7c7

Feng L, Tao D, Dong Z, et al. Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection. Biomaterials. 2017;127:13-24. doi:10.1016/j.biomaterials.2016.11.027

Ding H, Lv Y, Ni D, et al. Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed delivery for photodynamic therapy of cancer. Nanoscale. 2015;7(21):9806-9815. doi:10.1039/C5NR02470F

Gao C, Lin Z, Wu Z, Lin X, He Q. Stem-Cell-Membrane Camouflaging on Near-Infrared Photoactivated Upconversion Nanoarchitectures for in Vivo Remote-Controlled Photodynamic Therapy. ACS Appl Mater Interfaces. 2016;8(50):34252-34260. doi:10.1021/acsami.6b12865

Qiu WX, Zhang MK, Liu LH, et al. A self-delivery membrane system for enhanced anti-tumor therapy. Biomaterials. 2018;161:81-94. doi:10.1016/j.biomaterials.2018.01.037

Yang J, Teng Y, Fu Y, Zhang C. Chlorins e6 loaded silica nanoparticles coated with gastric cancer cell membrane for tumor specific photodynamic therapy of gastric cancer. Int J Nanomedicine. 2019;14:5061-5071. doi:10.2147/IJN.S202910

Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17(1):20-37. doi:10.1038/nrc.2016.108

Wang YF, Liu L, Xue X, Liang XJ. Nanoparticle-based drug delivery systems: What can they really do in vivo? Published online May 16, 2017. doi:10.12688/f1000research.9690.1

Xu L, Wu S, Wang J. Cancer cell membrane–coated nanocarriers for homologous target inhibiting the growth of hepatocellular carcinoma. J Bioact Compat Polym. 2019;34(1):58-71. doi:10.1177/0883911518819107

Aryal S, Hu CMJ, Fang RH, et al. Erythrocyte membrane-cloaked polymeric nanoparticles for controlled drug loading and release. Nanomed. 2013;8(8):1271-1280. doi:10.2217/nnm.12.153

Li S, Feng X, Wang J, et al. Polymer nanoparticles as adjuvants in cancer immunotherapy. Nano Res. 2018;11(11):5769-5786. doi:10.1007/s12274-018-2124-7

Qian H, Liu B, Jiang X. Application of nanomaterials in cancer immunotherapy. Mater Today Chem. 2018;7:53-64. doi:10.1016/j.mtchem.2018.01.001

Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun. 2016;7(1):13193. doi:10.1038/ncomms13193

Rao L, Meng QF, Huang Q, et al. Platelet–Leukocyte Hybrid Membrane-Coated Immunomagnetic Beads for Highly Efficient and Highly Specific Isolation of Circulating Tumor Cells. Adv Funct Mater. 2018;28(34):1803531. doi:10.1002/adfm.201803531

Kang T, Zhu Q, Wei D, et al. Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis. ACS Nano. 2017;11(2):1397-1411. doi:10.1021/acsnano.6b06477

Yang R, Xu J, Xu L, et al. Cancer Cell Membrane-Coated Adjuvant Nanoparticles with Mannose Modification for Effective Anticancer Vaccination. ACS Nano. 2018;12(6):5121-5129. doi:10.1021/acsnano.7b09041

Liang X, Ye X, Wang C, et al. Photothermal cancer immunotherapy by erythrocyte membrane-coated black phosphorus formulation. J Controlled Release. 2019;296:150-161. doi:10.1016/j.jconrel.2019.01.027

Wang C, Xu L, Liang C, Xiang J, Peng R, Liu Z. Immunological Responses Triggered by Photothermal Therapy with Carbon Nanotubes in Combination with Anti-CTLA-4 Therapy to Inhibit Cancer Metastasis. Adv Mater. 2014;26(48):8154-8162. doi:10.1002/adma.201402996

Cai J, Wang H, Wang D, Li Y. Improving Cancer Vaccine Efficiency by Nanomedicine. Adv Biosyst. 2019;3(3):1800287. doi:10.1002/adbi.201800287

Lopes A, Vandermeulen G, Préat V. Cancer DNA vaccines: current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res. 2019;38(1):146. doi:10.1186/s13046-019-1154-7

Huang ZH, Shi L, Ma JW, et al. a Totally Synthetic, Self-Assembling, Adjuvant-Free MUC1 Glycopeptide Vaccine for Cancer Therapy. J Am Chem Soc. 2012;134(21):8730-8733. doi:10.1021/ja211725s

Shen N, Wu J, Yang C, et al. Combretastatin A4 Nanoparticles Combined with Hypoxia-Sensitive Imiquimod: A New Paradigm for the Modulation of Host Immunological Responses during Cancer Treatment. Nano Lett. 2019;19(11):8021-8031. doi:10.1021/acs.nanolett.9b03214

Zhang R, Billingsley MM, Mitchell MJ. Biomaterials for vaccine-based cancer immunotherapy. J Controlled Release. 2018;292:256-276. doi:10.1016/j.jconrel.2018.10.008

Ganguly D, Haak S, Sisirak V, Reizis B. The role of dendritic cells in autoimmunity. Nat Rev Immunol. 2013;13(8):566-577. doi:10.1038/nri3477

Oth T, Vanderlocht J, Van Elssen CHMJ, Bos GMJ, Germeraad WTV. Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination. Mediators Inflamm. 2016;2016:e5740373. doi:10.1155/2016/5740373

Kroll AV, Fang RH, Jiang Y, et al. Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity. Adv Mater Deerfield Beach Fla. 2017;29(47). doi:10.1002/adma.201703969

Jiang Y, Krishnan N, Zhou J, et al. Engineered Cell-Membrane-Coated Nanoparticles Directly Present Tumor Antigens to Promote Anticancer Immunity. Adv Mater Deerfield Beach Fla. 2020;32(30):e2001808. doi:10.1002/adma.202001808




How to Cite

Hameed, Y., Nabi-Afjadi, . M., Gu, Y., & Wu, L. (2023). Cell membrane-coated nanoparticles for cancer therapy. Cancer Insight, 2(1), 145–162. https://doi.org/10.58567/ci02010009



Review Article