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Cell or Cell Membrane-Based Drug Delivery Systems

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Based on recent breakthroughs obtained in material science and nanotechnology areas, it is workable to design a drug carrier that can specifically deliver the drug to the disease area, such as liposomes, micelles, and nanoparticles (NPs). Liposomal drugs are already on the market. Liposomes, of which structure is alike to that of biological membranes, have the advantages of high biocompatibility, biodegradability, and size and surface manipulation competence. Drawbacks are that the cell membranes are too complex for the simple-structure liposomes to mimic. Therefore, scientists are thinking about using whole cell or cell derived vesicles (EVs) as drug carriers. Novel cell membrane-coated particles were developed in recent days that possess the advantages of natural cells and synthetic polymers.

The paper reviews the most up-to-date advances regarding cell or cell membrane-based DDS, mainly focused on whole cells, EVS, and cell membrane coated particles.

Whole Cell as Drug Carrier

Human cells have different physiological functions, including long circulation in the blood, site-specific migration, and physical barriers crossing. Some types of cells with retained cell structure and function can be used as drug carriers. RBCs, SCs, and immunological cells RBC are hotspots as drug carriers.

RBC as Drug Carrier

The most frequently used whole cells as drug carriers for various bioactive agents are carrier RBCs that are intensively investigated in the past decades and some have undergone clinical tests. Superior to artificial DDS, RBC is intrinsically biocompatible, biodegradable, and non–immunogenic.

Stem Cells–based Drug Carrier

Several kinds of SCs, such as MSCs and neural stem cells (NSCs), have been verified to have the competence to migrate towards tumor microenvironment, which are widely applied in tumor-specific drug delivery. For example, MSCs containing multifunctional silica NPs were applied in the tumor multimodality imaging, including optical, PET, and MR imaging. However, SCs have the risk of promoting tumor growth or even differentiating into tumor. It's critical to select SC type carefully when designing the SC-based delivery system.

Other Cell-based Drug Carrier

As tumor tissue can recruit immune cells, macrophages, neutrophils, and lymphocytes can be used as DCs, which, after loaded with therapeutic agents ex vivo, can be phagocytosed by macrophages and accumulate in tumor tissue or even migrate through the blood-brain barrier (BBB) into brain tumors.

Extracellular Vesicle-Based DDS

EVs, small vesicles secreted by eukaryotic cells, can deliver biologicals to affect the function of the receiving cells, which can be categorized into microvesicles (MVs), membrane particles, exosome-like particles, apoptotic vesicles, and exosomes.

Shedding Vesicles

Included in this type are RBC-derived microvesicles, tumor cell-derived microparticles, MSC-based microvesicles, and other extracellular vesicles.

Exosomes

Exosomes mediate biological immune response and provide new functional properties to the recipient cells, which are natural vehicles of protein and genetic materials with targeting properties, and therefore the perfect candidates for exogenous therapeutic agent delivery, especially when they are genetically modified. Exosomes are mainly applied in immunotherapy and drug delivery.

Cell Membrane Coated Particles for Drug Delivery

Cell membrane coated NPs were developed by the researchers, which can load hydrophobic agents, co-deliver drugs with different properties, fulfill the well-controlled release, and most important of all, prevent from being cleared by the body.

RBC Membrane Coated NPs

Owing to the breakthrough of Zhang's group in 2011 in the RBC membrane (RBCm) technology, RBC membrane cloaked NPs (RBC-NPs) were produced, which are recently thought of holding the function as the vaccine.

Other Eukaryocyte Membrane Coated Particles

Eukaryocyte has a more complicated structure with a variety of physiological functions. By now, cancer cell membrane-coated PLGA NPs and leukocyte membrane-coated nanoporous silicon particles are the eukaryocyte membrane coated particles that have been investigated, which can perform natural properties and parent cells bio functions. There still needs further research as support.

There are still limitations in the clinical translation of the above-mentioned drug carriers, including difficulty to fulfill the location release of RBC, genetic risk of stem cells, and insufficient studies of EVs and cell membrane coated NPs, and exorbitant costs. It still needs more research supported by multidisciplinary investigations.

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