Cell membrane-coated nanoparticles: a novel multifunctional biomimetic drug delivery system

Abstract

Recently, nanoparticle-based drug delivery systems have been widely used for the treatment, prevention, and detection of diseases. Improving the targeted delivery ability of nanoparticles has emerged as a critical issue that must be addressed as soon as possible. The bionic cell membrane coating technology has become a novel concept for the design of nanoparticles. The diverse biological roles of cell membrane surface proteins endow nanoparticles with several functions, such as immune escape, long circulation time, and targeted delivery; therefore, these proteins are being extensively studied in the fields of drug delivery, detoxification, and cancer treatment. Furthermore, hybrid cell membrane-coated nanoparticles enhance the beneficial effects of monotypic cell membranes, resulting in multifunctional and efficient delivery carriers. This review focuses on the synthesis, development, and application of the cell membrane coating technology and discusses the function and mechanism of monotypic/hybrid cell membrane-modified nanoparticles in detail. Moreover, it summarizes the applications of cell membranes from different sources and discusses the challenges that may be faced during the clinical application of bionic carriers, including their production, mechanism, and quality control. We hope this review will attract more scholars toward bionic cell membrane carriers and provide certain ideas and directions for solving the existing problems.

Keywords: Applications; Cell membrane; Challenges and prospects; Drug delivery systems; Nanoparticle.

Fig. 1

Timeline of CMC-NPs development

Fig. 2

A schematic diagram of preparing monotypic cell membrane-coated nanoparticles. Step 1 includes two processes of harvesting cell membrane fragments; step 2 requires cautious selection and fabrication of the inner core according to the purpose; step 3 is the final step to coat the cell membrane onto a template. Created with BioRender.com

Fig. 3

a Schematic illustration of the vesicle extrusion process for liposome preparation. Reproduced with permission [70]. Copyright 2005, Small. b Schematic illustration of the camouflage of cell membrane to nanoparticles by sonication. c Microfluidic electroporation facilitates the synthesis of RBC membrane-capped magnetic nanoparticles (RBC-MNs). Reproduced with permission [78]. Copyright 2017, ACS Nano

Fig. 4

Schematic of different synthesis methods. a Separately extracted cell membranes and then fused two membranes. b Cells fused first, and obtain hybrid membrane from the fused cell. Created with BioRender.com

Fig. 5

Characterization of HCMN. a SDS-PAGE protein analysis of HCMN. b Western blot analysis for HCMN. c Immunogold TEM images of HCMN (scale bars = 50 nm). Reproduced with permission [52]. RBCm, RBC membrane; [RBC-P]m, RBC–platelet hybrid membrane; Pm, platelet membrane; RBCNP, RBC membrane-coated nanoparticle; [RBC-P]NP, RBC–platelet hybrid membrane-coated nanoparticle; PNP, platelet membrane-coated nanoparticle Copyright 2017, Advanced Materials

Fig. 6

a A schematic illustration of the advantages of MNPs. Created with BioRender.com. b Fluorescence imaging of mice after in vivo injection of Rhd B-labeled MPCM-camouflaged MSNCs or bare MSNCs through the tail vein of mice in 48 h. Reproduced with permission [23]. Copyright 2015, Advanced Healthcare Materials. c Representative fluorescence images of cellular uptake of tumor-associated macrophage membrane-coated nanoparticles or liposome-coated nanoparticles (red fluorescence) in 4T1, L929, or primary macrophages. Reproduced with permission [150]. Copyright 2021, Nano Letters. d Fluorescence intensity of MNP in different organs. n = 3, *p < 0.05. Reproduced with permission [154]. Copyright 2019, Nano Letters

Fig. 7

a Synergistic photothermal of cancer. Created with BioRender.com. b Temperature increases of water, Fe₃O₄, ICG, Fe₃O₄-ICG, and Fe₃O₄-ICG@IRM with NIR irradiation (808 nm, 1.0 W/cm², 10 min). Reproduced with permission [176]. Fe₃O₄-ICG@IRM, IRM (ID8 ovarian cancer cell membrane-RBC membrane) camouflaged ICG-loaded magnetic nanoparticles; Fe₃O₄-ICG, ICG-loaded magnetic nanoparticles. Copyright 2021, ACS Nano

Fig. 8

DiRL labeled liposomal nanoparticles (DiRL, LM-DiRL, TM-DiRL, and LTM-DiRL) (n = 4). a In vivo biodistribution of different groups after intravenous injection. b Quantitative analysis of fluorescence accumulation in the main organs. c Histogram of quantitative analysis of fluorescence accumulation in the main organs. Reproduced with permission [28]. DiRL, DiR-labeled liposomal nanoparticles; LM-DiRL, leukocyte membrane-coated DiRL; TM-DiRL, tumor cell membrane-coated DiRL; LTM-DiRL, leukocyte-tumor cell membrane-coated DiRL. Copyright 2018, Nano Letter