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Review
. 2018 Jun;30(23):e1706759.
doi: 10.1002/adma.201706759. Epub 2018 Mar 27.

Cell Membrane Coating Nanotechnology

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Free PMC article
Review

Cell Membrane Coating Nanotechnology

Ronnie H Fang et al. Adv Mater. .
Free PMC article

Abstract

Nanoparticle-based therapeutic, prevention, and detection modalities have the potential to greatly impact how diseases are diagnosed and managed in the clinic. With the wide range of nanomaterials available, the rational design of nanocarriers on an application-specific basis has become increasingly commonplace. Here, a comprehensive overview is provided on an emerging platform: cell-membrane-coating nanotechnology. As a fundamental unit of biology, cells carry out a wide range of functions, including the remarkable ability to interface and interact with their surrounding environment. Instead of attempting to replicate such functions via synthetic techniques, researchers are now directly leveraging naturally derived cell membranes as a means of bestowing nanoparticles with enhanced biointerfacing capabilities. This top-down technique is facile, highly generalizable, and has the potential to greatly augment existing nanocarriers. Further, the introduction of a natural membrane substrate onto nanoparticles surfaces has enabled additional applications beyond those traditionally associated with nanomedicine. Despite its relative youth, there exists an impressive body of literature on cell membrane coating, which is covered here in detail. Overall, there is still significant room for development, as researchers continue to refine existing workflows while finding new and exciting applications that can take advantage of this developing technology.

Keywords: biomimetic nanomedicine; detoxification; drug delivery; immunotherapy; medical imaging.

Figures

Figure 1
Figure 1
Cell membrane-coated nanoparticles. A variety of cell types have been used as sources of membranes to coat over nanoparticles. Each cell membrane type can utilize unique properties to provide functionalities to nanoparticulate cores, the material of which can be varied depending on the desired application.
Figure 2
Figure 2
RBC membrane-coated nanoparticles. Cell membrane can be derived from RBCs using hypotonic treatment. When co-extruded with polymeric nanoparticulate cores, RBC membrane-coated nanoparticles are formed. The nanoparticles retain many of the same surface markers as the original RBCs, including the self-marker CD47 that allows for immune evasion and long blood circulation. Reproduced with permission.[23] Copyright 2011, National Academy of Sciences.
Figure 3
Figure 3
RBC membrane-coated gold nanocages for photothermal therapy. RBC membrane coating allows gold nanocages to circulate longer in the bloodstream and accumulate in tumors efficiently. When irradiated with an NIR laser, the nanocage cores raise the local temperature, thus enabling control of tumor growth. Reproduced with permission.[69] Copyright 2014, American Chemical Society.
Figure 4
Figure 4
RBC membrane-coated nanosponges for toxin neutralization. Pore-forming toxins can insert into the RBC membrane on the surface of the nanosponges, where they are retained and neutralized. By safely sequestering the toxins, RBC nanosponges spare healthy RBCs from being lysed. Reproduced with permission.[79] Copyright 2013, Nature Publishing Group.
Figure 5
Figure 5
RBC membrane-coated nanotoxoids for antivirulence vaccination. a) Nanotoxoids are fabricated by inserting pore-forming toxins into RBC membrane-coated nanoparticles, a process that neutralizes their toxicity. Reproduced with permission.[86] Copyright 2013, Nature Publishing Group. b) Without protective immunity, subcutaneous injection of MRSA bacteria will cause the formation of skin lesions. c) After immunization, the immune system produces antibodies that can neutralize toxins and lessen cell damage at the site of infection, reducing bacterial colonization and invasiveness. Reproduced with permission.[87] Copyright 2016, Wiley-VCH.
Figure 6
Figure 6
Platelet membrane-coated nanoparticles (PNPs) for biointerfacing. Nanoparticles coated with platelet membrane can utilize a unique set of transferred surface integrins and markers to evade the immune system and bind to sites that naturally recruit platelets. PNPs can deliver antineoplastic drugs to damaged vasculature by binding to exposed collagen and can kill pathogens by binding to them and releasing loaded antibacterial drugs. Reproduced with permission.[24] Copyright 2015, Nature Publishing Group.
Figure 7
Figure 7
Platelet membrane-coated magnetic nanoparticles for combination MRI imaging and photothermal therapy. The retention of self-marker CD47 on the platelet membrane coating reduces the macrophage uptake of PNPs, allowing for long circulation of the particles and passive tumor accumulation via the enhanced permeation and retention effect. The high concentration of the coated iron oxide cores in the tumor can be used for MRI imaging of the tumor location and photothermal therapy for cancer cell killing. Reproduced with permission.[95] Copyright 2017, Wiley-VCH.
Figure 8
Figure 8
Platelet membrane-coated nanoparticles for clearance of pathological antibodies. a) Platelet-derived membrane vesicles are coated onto polymeric nanoparticle cores. b) In autoimmune thrombocytopenia, endogenous antibodies against platelets facilitate their clearance by macrophages. c) Platelet membrane-coated nanoparticles can serve as decoys and bind to anti-platelet antibodies. Absorption of the pathological antibodies spares native platelets, reducing the severity of disease. Reproduced with permission.[96] Copyright 2016, Elsevier Ltd.
Figure 9
Figure 9
Leukocyte membrane-coated particles. Porous silicon microparticles can be functionalized with positively-charged surface groups to facilitate surface coating with leukocyte membrane. The coated particles retain the ability to home to tumors and transverse across inflamed endothelium using surface markers inherent on white blood cells. Reproduced with permission.[97] Copyright 2012, Nature Publishing Group.
Figure 10
Figure 10
Macrophage membrane-coated gold nanoshells for photothermal therapy. a) Macrophage cells are used as the source for membrane vesicles, which can be used to form a coating around gold nanoshells. b) The macrophage membrane coating can shield gold nanoshells from macrophage uptake and facilitate enhanced tumor accumulation. The gold nanoshell cores can generate hyperthermia upon laser irradiation for tumor ablation. Reproduced with permission.[103] Copyright 2016, American Chemical Society.
Figure 11
Figure 11
Antibody-decorated leukocyte membrane-coated magnetic nanoclusters for circulating tumor cell enrichment. Azide-functionalized leukocyte membrane can be coated onto iron oxide nanoclusters and subsequently bind modified antibodies onto the membrane surface. Particles decorated with an anti-EpCAM antibody attach to circulating tumor cells in blood samples, and the bound target cells can then be isolated by magnetic extraction. The leukocyte membrane coating prevents nonspecific binding to other white blood cells in the sample for reduced contamination of the purified circulating tumor cells. Reproduced with permission.[106] Copyright 2016, Wiley-VCH.
Figure 12
Figure 12
Cancer cell membrane-coated nanoparticles for anticancer vaccination and homotypic targeting. Polymeric nanoparticles coated with cancer cell membrane can deliver a wide range of cancer surface antigens to immune cells for processing and training against cancer cells. The cancer cell membrane also contains homotypic adhesion molecules that are retained onto the nanoparticles after coating for targeted tumor delivery. Reproduced with permission.[25] Copyright 2014, American Chemical Society.
Figure 13
Figure 13
Cancer cell membrane-coated nanoparticles for targeted cancer drug delivery. Surface markers like Thomsen–Friedenreich antigen, E-cadherin, CD44, and CD326 can be transferred onto the surface of cancer cell membrane-coated nanoparticles to target to tumors of the same cancer type. When loaded with anticancer drugs like PTX, the CCNPs preferentially bind and release the drugs to cancer cells in the primary tumor as well metastatic tumors. Reproduced with permission.[108] Copyright 2016, Wiley-VCH.
Figure 14
Figure 14
Cancer cell membrane-coated upconversion nanoparticles for tumor imaging. Upconversion nanoparticles coated with cancer cell membrane have long blood residence due to immune escape, and can specifically target homologous cancer cells in vivo due to adhesion markers present on the cell membrane. When administered intravenously, the cancer cell membrane-coated nanoparticles actively migrate to the tumor site and emit strong luminescence under NIR irradiation. Reproduced with permission.[111] Copyright 2016, Wiley-VCH.
Figure 15
Figure 15
Cancer cell membrane-coated nanoparticles for antitumor vaccination. Polymeric nanoparticles encapsulating the adjuvant CpG ODN 1826 can be coated with cancer cell membrane as a rich source of antigenic material. CCNPs can facilitate the delivery of CpG to its endosomal receptor for dendritic cell maturation, and the co-delivered membrane provides cancer antigens for presentation. Downstream immune processes yield the generation of T cells specific for multiple cancer surface antigens, which can subsequently detect and eliminate tumors. Reproduced with permission.[118] Copyright 2017, Wiley-VCH.
Figure 16
Figure 16
Cardiac stem cell membrane-coated growth factor-loaded nanoparticles for tissue repair. Stem cell membrane coating provides the polymeric nanoparticle cores with a binding affinity for sites of injury, such as injured cardiomyocytes after a heart attack. Upon binding, the nanoparticles release loaded growth factors to promote tissue repair through cell proliferation angiogenesis, and remuscularization. Reproduced with permission.[122] Copyright 2017, Nature Publishing Group.
Figure 17
Figure 17
Stem cell membrane-coated upconversion-silica core-shell nanoparticles for photodynamic therapy. Mesoporous silica shells loaded with photosensitizers is coated with bone marrow-derived mesenchymal stem cell membrane to gain tumortropism. The coated particles can efficiently accumulate in tumors after in vivo application, and the high local concentration of photosensitizers in tumor tissue enables enhanced photodynamic therapy and cancer cell killing. Reproduced with permission.[124] Copyright 2016, American Chemical Society.
Figure 18
Figure 18
Beta cell membrane-coated nanofibers for enhancing cell proliferation and function. Electrospun PCL nanofiber scaffolding coated with beta cell membrane can encourage the proliferation of their source cells through direct cell membrane-to-cell contact. The cell membrane coating transferred beta cell-specific proteins onto the nanofiber surface, and beta cells cultured on the fibers showed increased insulin production and cell proliferation. Reproduced with permission.[126] Copyright 2016, The Royal Society of Chemistry.
Figure 19
Figure 19
Bacteria membrane-coated nanoparticles for modulating antibacterial immunity. Bacteria-secreted outer membrane vesicles contain a variety of bacterial surface antigens, and coating the membrane material onto gold nanoparticles facilitates the intracellular delivery of the antigens to dendritic cells. After vaccination, the nanoparticles can induce dendritic cell maturation and the generation of high antibacterial titers. Reproduced with permission.[127] Copyright 2015, American Chemical Society.
Figure 20
Figure 20
RBC-platelet fusion membrane-coated nanoparticles for enhancing nanoparticle functionality. RBC membrane fused with platelet membrane can be coated onto polymeric nanoparticles and retain cell specific functionalities of both parent cell types. Reproduced with permission.[132] Copyright 2017, Wiley-VCH.

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