Cell Membrane Coated Nanoparticles for Biomedical Applications
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Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
J. Adv. Appl. NanoBio Tech.
ISSN: 2710-4001
Journal web link:
http://www.AANBT.dormaj.com
https://doi.org/10.47277/AANBT/3(1)59
Cell Membrane Coated Nanoparticles for
Biomedical Applications
Elham Nemati1, Ahmad Gholami1*
*Biotechnology Research Center, Shiraz University of Medical Science, Shiraz, Iran
Received: 20/12/2021 Accepted: 26/12/2021 Published: 20/03/2022
Abstract
Today cell-based remedies have shown amazing and hopeful results in many medical fields, including genetic engineering, bio-
imaging, and regenerative medicine and drug delivery. The distribution of phospholipids and proteins across cellular membranes
is asymmetric in most organisms and this asymmetry plays an essential role in various cellular activities and functions, for example
programmed cell death, absorption, etc. Scientists have attempted to study membrane-regulated formation and function for many
years. Today, researchers are constantly trying to use asymmetric artificial membrane models in various fields. Presently
nanoparticles (NPs) have been extensively inquired into several biomedical applications containing diagnostics, cancer therapy,
imaging, and targeted drug and gene-delivery. It is necessary to modify the surface of nanomaterials and nanoparticles so that they
are not to be cleared by the immune system. In this study, biomedical applications and challenges faced by nanoparticles coated by
cell membranes and other medical applications of asymmetric membranes which are often made of lipids, polymers, or a
combination of both, are investigated.
Keywords: Nanoparticles, biomedical applications, Cell Membrane-Coated Nanoparticles, targeted drug delivery, immune responses
1 Introduction many fields such as targeted drug delivery, diagnostic
imaging, etc. Because of the great properties of
The cell membrane is made of lipids, proteins and nanoparticles, they can control drug releasing, protect drugs
carbohydrates and is semi-permeable and it also varies based and also loading capacity and targeting ability, etc. So they
on cell function in different cells. 1, 2 The lipid molecules have shown great potential for the future of biomedical
made bilayers that prepare a steady substrate, and proteins applications. 1, 10 Nanoparticles protect loading until target
and channels can accomplish their cellular activities and delivery, also with altering their ligands we could enhance
transport materials with selective permeability. 1, 3 One of the their ability like targeting. 11, 12
important functions of the cell membrane is cellular
communication through information transmission and We could use Polyethylene glycol (PEG) to extend
reception. 1 The plasma membrane also acts as a border and nanoparticles circulation time but it’s not a permanent
swaps information between cell and another cell, or between solution, and also can cause hypersensitivity. 11, 13 Therefore
cell and environment. 4, 5 Cell membranes have specific cell membrane coating is so promising approach. Until today
receptors so specific biomolecules can bind them. 1 When cell membrane coating imitates the surfaces of bacteria, stem
we coated nanomaterials with cell membranes that have cells, platelets, cancer cells, RBCs, and leukocytes. 6, 11
these specific receptors, biomolecules identify them. Cell Different antigenic profiles on cell membranes help them to
membrane coated nanomaterials provide functions and perform diverse biological functions. 1, 14 Because of its good
performances of live cells for them, which can use in biocompatibility, the ability to do various functions, and no
different biomedical applications. 1, 6 need for organic solvents, Used in various medical
technologies, e.g. immunotherapy, optical therapy, tumor
The most of nanoparticles that use in nanomedicine, are imaging, drug delivery, vascular injury repair,
synthetic, and the immune system discovers them simply detoxification, etc. (figure 1.) and the design and biomedical
and removes them. 7, 8 Scientists cover nanoparticles with applications of cell membrane-coated nanomaterials discuss
cell membranes so they could stay longer in the body without in this review. 1, 11
discovering and eliminating. 7, 9 We can use Nanoparticles in
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Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
Figure 1. Some of the applications’ of membrane coated nanoparticle in biomedical fields. (Reposted with permission from
reference 11 Copyright © 2019, The Author(s))
2 Cell membrane 2.3 Cell membrane`s proteins
The total membrane area in a body is about 107 m2. 15 Cell Cell membrane`s proteins accomplish most of the vital
membrane is made of lipids, transmembrane proteins, and performance such as, cell-cell recognition, transportation
peripheral proteins, carbohydrates, glycoproteins, and interactions. 7 Membrane receptor proteins particularly
glycolipids, and semipermeability is one of its important perform interactions between different cells and also
features. 1, 15 Just as the function of different cells is different, between cells and environment.
the structure of their cell membranes is also different. The
cell membrane protects the entirety and cell shape and it also 3 Using asymmetric cell membranes in medical
controls cell entry and exit, and it is also responsible for applications
cellular communication. 1, 16
Overall because of all the amazing features of the cell
2.1 Cell membrane`s lipids membrane has for example shape of that, membrane
channels, chemical components, receptors, and also their
Cell membrane mostly contains lipids, they constitute two numerous functions, and its Biocompatibility, it is currently
leaflets that together form a bilayer because of their the best and most ideal example for coating nanoparticles
amphiphilic character. 17, 18 Lipids’ hydrocarbon chains face and other medical applications. 15, 21 Cell membranes can
each other and create the core of the membrane; and their prepare stable segments on which proteins can support
polar head group is oriented to the surroundings. 17, 19 signaling and selective transmission. 15 With coating
Asymmetry in natural membranes is mainly due to the nanomaterials with the cell membrane, functions and
distribution of lipids, and also they play a major role in signal features of live cells are transferred to nanomaterials, and
transduction and molecular recognition processes and are with using different kind of cells, functions and features of
used to store energy. nanomaterials will be different. 1, 15 So because of the
features mentioned earlier we can widely use cell membrane
2.2 Cell membrane`s carbohydrates in different biomedical applications, for instance vesicles
that use in drug delivery or gene delivery, biosensors. 9, 15
Another important ingredient from which cell membranes
are made is carbohydrates, they are usually combined with 4 Coating Methods
proteins and lipids in glycoconjugate form. 7 These
substances are involved in cell signaling proceedings, Various methods are used to manufacture cell membrane-
predominantly in cell recognition processes as receptors. 7 coated nanoparticles, first with physical extrusion
Monosaccharides, which are the smallest type of membrane nanoparticles cores and purified membrane are coextruded.
10, 22 Lately sonication-based method has been applied. In
carbohydrates, contain mannose, fructose, galactose, sialic
acid, glucose, are used in the production of nanoparticles for this method, due to the intense forces created by ultrasonic
specific targeting ability and also their mediate role in energy, the core-shell nanoparticles are formed
cellular responses. 7, 20 automatically. 19, 22 In this method, fewer materials are used
than the previous method. 22, 23 Researchers reported some
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Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
new approaches to make membrane-coating nanoparticles for transferring oxygen with hemoglobin to distal sites in
with electroporation and use RBC membrane for coating each cell. 26, 27 11 There are some self-markers on RBC
magnetic nanoparticles. 21, 22 If we adjust the pulse voltage, membranes that keep the nanoparticles safe from blood
duration and the flow velocity correctly, high-quality cell clearance and let them remain in blood circulation about 120
membrane nanoparticles are obtained from this technique. 22, days. 28 29 Different types of particles like metal–organic
24, 25 Besides all of these methods we can also use live cell to frameworks (MOFs), mesoporous silica nanoparticles
produce them. And after some changes force cells to secrete (MSNs), poly (lactic-co-glycolic acid) (PLGA)
vesicles containing the exogenous nanoparticles. 22, 24 nanoparticles, gold nanoparticles, perfluorocarbons (PFCs)–
PLGA nanoparticles, Fe2O3 NPs can be covered by RBC
5 Choosing appropriate cell membranes. (figure 2.) 23, 29, 30 RBC is completely
biocompatible to deliver antiviral, anti-inflammatory, anti-
Circulatory cells are the best choices for coating since their
neurodegenerative and anti-cancer drugs. 14, 31 Especially in
perfect properties, including natural delivery mechanisms,
cancer they are so useful and with the long circulation time
circulation throughout the body, the ability to pass almost
in the bloodstream, Therefore, it can be more effective in
impermeable biological barriers and natural stealth
treating cancer and delivering drugs to cancer tissue than
properties. 13, 26 So for choosing the best cell for the specific
conventional drugs and Increase the effect of drug
application it's critical to know cell functions and features
localization in vivo. 29, 30 Gold nanoparticles` effect and their
entirely. 26
photothermal, also have been investigated And the results
6 RBC Coated Nanoparticles were satisfactory so far. 5, 30 And with the use of membrane-
coated PLGA NPs increasing the efficiency of antigen
Red blood cells or Erythrocytes are the greatest choices for delivery to dendritic cells have been observed in the new
coating, they are the most plentiful blood cell that are vital research. 30, 32
Figure 2. Some of the nanoparticles that can be loaded in RBC membranes. (Reposted with permission from reference 29
Copyright © 2019, Oxford University Press)
Coating NPs with RBC membrane cause, improving in progressions and atherosclerosis, etc. 34, 35 Platelet
stability and solubility, decrease adverse effects and as membrane contains their own various biomarkers such as
mentioned earlier lengthen blood circulation without CD47 that help them to survive from being phagocytosis by
recognizing by macrophages and immune system, macrophage, and some other biomarkers that inhibit
tolerability, reduced immunogenicity.11, 28, 31 Also due to activation of immune and complement system. 34, 36
semi-permeability the release process is slow and continues. According to some reports platelet membrane‑coated
11, 33 So it could improve therapeutic influence in numerous
nanoparticles can aim collagen, foam cells, inflammatory
methods. 28 Therefore membranes` of erythrocyte were the tissues and activated endothelium. 37 34 38, 39 Tumors imbibe
first and attractive choice for coating. 22 platelets and make a shield to conceal their surface antigens
from the immune system, so if antitumor drugs load in
platelets membrane, they could directly be absorbed into the
7 Platelets Coated Nanoparticles tumor site and reduce the metastasis of lung cancer and
prevent primary growth of nodules in breast cancer. 34, 40-44
Platelets are non-nucleated cells in the blood that perform In addition, antibiotics also can be loaded in platelets
some of the essential pathophysiological processes, such as membrane like vancomycin, and improved antimicrobial
Role in body functions against inflammation, tumor efficacy in vivo. 34 45, 46
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Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
8 WBC Coated Nanoparticles 9 Macrophage Coated Nanoparticles
Leukocyte are immunological cells defending body and Macrophages are important cells in the immune system that
native cells against pathogens and diseases. 11 Leukocyte resident in tissue, they have taken from monocytes and
membrane‑coated nanoparticles have advantages over red recruited and digest harmful microorganisms and other non-
blood cells such as they are larger than RBCs, because of native substances that have entered the body. 29, 30 Cytokines
their amoeboid moving can move between blood flow and and chemokines secreted by damaged tissue send signals to
surrounding tissue effectively. 11, 47 They also have particular circulating monocytes, which become macrophages when
surface proteins and membrane receptors which make them they reach the tissues from the bloodstream. 30, 49 Monocytes
extremely useful. 44 Leukocyte can pass through the are kind of leukocytes (WBC) they have key roles in
endothelium so leukocyte Membrane‑Coated Nanoparticles inflammation and homeostasis. 31 Some of the advantages of
also traverse the inflamed endothelium and carry the using macrophages (monocytes) for carrying drug delivery
nanoparticles with themselves. 41, 48 is they can cross complicated biological barriers so they can
easily migrate and interpenetrate into inflammatory tissues
Lymphocytes, monocytes, neutrophils, eosinophils, and and tumors; (figure 3.) and also because of their long
basophils are different kind of leukocytes and because they lifecycle nanoparticles remain in the body longer and
have nucleus using them as membrane are more difficult perform their duties. 31, 36 Studies and experiments until now
than RBCs and platelets. 11, 20 Because their attractive showed promising future for the treatment of cancer and
properties they can simply interact with tumor cells both in anticancer immune activation. 11, 31 Macrophage membrane
the tumor site and in circulation. 11 We can use membrane of coated nanoparticles are also used for the treatment of sepsis
macrophage, monocyte, T lymphocyte, natural killer cell and that is a kind of uninhibited systemic inflammatory response
other type of white blood cells depending on the needs, to bacterial infections. 1, 50 They act like decoys and bind to
features and characteristics we need. Macrophages, for endotoxins and cytokines and control immune activation and
example, are described below. inflammation. 1
Figure 3. Emtansine liposome coated with macrophage membrane for suppressing lung metastasis of breast cancer. (Reposted
with permission from reference 51 Copyright © 2016, American Chemical Society)
10 Stem Cell Coated Nanoparticles CX3CL1 (T-cell attractant) for cancer therapy. 34, 57 Stem
cell coated nanoparticles can act specifically on the tumor,
Mesenchymal stem cells (MSCs) or stem cells can multi- so their use as drug carriers reduce and decrease the systemic
differentiate and self-renovate and the ability to attaining toxicity and side effects of chemotherapy. 30, 53, 58-62 Also
features easily. 30, 52-54 (figure 4.) They have been used as the during ischemic injury (like myocardial infarction) stem cell
treatment of numerous diseases in many clinical trials coated nanoparticles can cure the injury more rapidly with
because of their higher tot potency and indefinite lifespan. 16, improved blood reperfusion, muscle repair, limb salvage and
34, 52, 55, 56 MSCs can carry interferons, interleukins, and enhancing the retention time in injured tissues. 30, 63, 64
Figure 4. Preparing stem cell membrane derived vesicles from mesenchymal stem cells. (Reposted with permission from
reference 65 Copyright 2016, American Chemical Society.)
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Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
11 Cancer Cell Membrane-Coated Nanoparticles One of the most important properties that nanoparticle with
the bacterial and viral membranes is their interaction with
Malignant cells have some features that make them one of their target cells and bypassing immune responses. 30, 70, 71
the main sources of membrane. 22 They could be easily (figure 5.) Some Bacteria have the ability to target tumors
cultured in vitro and their robustness, the ability to self-target naturally including Clostridium beijerinckii, Bifido
(that can use in delivery of cancer drug delivery and bacterium bifidum and S. Typhimurium. 30 For example,
imaging), their immune escape ability and homotypic nanoparticles coated with Salmonella membranes reduced
binding capacities, make them a major choice. 22, 66-68 The melanoma size in mice. 72, 73 Another experiment was used
effect of membrane coated nanoparticles which from the Salmonella typhomurium membrane and it was found that
same source cell significantly increase. 22, 69 Also, the tumor growth and cancer metastasis were significantly
magnetic field can be used to guide nanoparticles to the reduced. 74 Viruses are also used for targeted drug delivery,
tumor site. 22, 66 Cancer membrane coated nanoparticle viruses produce capsids that have the self-assembled ability
provides powerful tools for researchers to improve the and for this purpose, it is used. 30 Drugs and nanoparticles
intracellular transferring and the subcellular targeting for replace genetic material in capsids, they are used for
chemotherapy, localized phototherapy, intensified imaging. photodynamic therapy and optical imaging such as MRI. 20,
66, 68
54, 75
12 Microorganisms (bacteria and viruses) as Membrane
of Nanoparticles
Figure 5. Bacteria membrane coated nanoparticles containing bacterial surface antigens. (Reposted with permission from
reference 71 Copyright 2015, American Chemical Society.)
13 Hybrid Cell Membrane-Coated Nanoparticles delivery of cytotoxic drugs and photosensitizers. 81, 82 Using
hybrid membranes in comparison with single membrane-
Hybrid membranes are made from a combination of different coated nanoparticle showed promising results and better
membranes of multiple cells, and they improved the uptake, deeper tumor penetration, and better immune
functional characteristics of coated nanoparticles. 76 32, 77 escaping. 76, 81, 83 Recently studies have shown that cancer
First of all different membranes derive from the target cells cell coated nanoparticles that hybridized with RBC, platelets
and then fuse all the membranes with mechanical forces such (figure 6.), stem cell and leukocytes membranes, increased
as stirring, sonication or extrusion, or at first fuse live cells. their half-life and longevity and accumulation at the tumor
76, 78, 79 For example, RBC membranes hybridize platelet
site, as well as the length of time they remain in the
membranes were used for cancer therapy. 80 Also, platelet bloodstream dramatically.83, 84
membranes hybridize with neutrophil membranes for the
53Advances in Applied NanoBio-Technologies 2022, Volume 3, Issue 1, Pages: 49-59
Figure 6. Cancer membranes hybridize platelet membranes were used for cancer theranostics. [CSC-P]MNs were also used for
enhanced in vivo tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT) for their magnetic property and
optical absorption ability. (Reposted with permission from reference 84 Copyright 2019, Wiley-VCH.)
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