Research of Cell Membrane Nano Drug Delivery System and Its Application in Bionic Nanomedicine

Most of the old drugs are currently limited in their effectiveness because of poor pharmacokinetics, simple clearance by the body and cytotoxicity. Nanoparticle technology in particular, Nano drug delivery system is getting a lot of attention and application in medicine in the recent years. Since it is small (1100nm), targets well, and stays in the circulation long enough, NPs are a good candidate as a drug carrier, enabling an enhanced in vivo targeting capability and less nonspecific adverse effects to some degree. But there are also a lot of problems in the clinical use of NPs. NPs, for instance, once inserted into the body will be assessed and excised by the body’s innards as foreign substances that generate immune responses and toxic effects. The NP recognition by the immune system and NPs synthesis by the reticuloendothelial system are the primary barriers to nano drug delivery to organs, tissues and lesions. Also, NPs have a negative side effect, like microcirculatory embolism. Nano medicine clinical trials have, after all, failed. It is a need for a new technology to make this drug delivery system better.

Research suggests that PEG added to the surface of NPs will create a hydration layer and increase the spatial stability of NPs. Even though PEG-modified NPs will still cause immune rejection responses to some degree in the body, the “stealth coating” inspired researchers. Then, researchers imprinted the biofilm with nanomedicines, increasing targeting power without the rejection and other side effects. Today, it is possible to produce different kinds of cell membrane-encapsulated nanoparticles — for example, red blood cell membrane nanoparticles, white blood cell (neutrophil, macrophage) membrane nanoparticles, platelet membrane nanoparticles, tumor cell membrane nanoparticles, stem cell membrane nanoparticles, bacterial outer membrane vesicle nanoparticles, etc. This bionic nanostructure has proven effective for drug delivery, detoxification, photothermal treatment, imaging, cancer diagnosis, immune surveillance, vaccine design, etc. This paper presents the most recent research advances of cell membrane nanodrug delivery systems for bionic medicine.

Application of Different Types of Cell Membranes in Bionic Nanomedicine

Erythrocyte Membranes in Bionic Nanomedicine

They’re the largest cell group in blood, the main transporter of oxygen and nutrients. Erythrocytes have a typical lifespan of about 120 days, so they are the best material for long-circulating NPs. NPs wrapped in erythrocyte membranes keep the CD47 transmembrane protein on the erythrocyte membrane; this is a cell-surface glycoprotein molecule that can attach to integrins, thrombospondin-1, and signal regulatory protein (SIRP). When CD47 and SIRP- receptors co-operate, they can stop macrophage phagocytosis and “don’t eat me” signals, making the nanoparticles extremely biocompatible. Others synthesized and shaped RBCNPs (red blood cell membrane-encapsulated nanoparticles), and targeted the excised red blood cell membranes twice, with DWSW peptide and asparagine-glycine-arginine (NGR) peptide. The dual-purpose mutated membranes of red blood cells improved NPs’ binding to brain and tumour cells and contained PLGA particles encoding Euphorbia factor L1. This combined entity is able to cross the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB) with systemic injection, and to be targeted to glioma lesions. It has been established in vivo and in vitro experiments and reviews that dual-target peptide-modified RBCNPs exhibit better targeted uptake of gliomas than nanoparticle-based drug delivery systems, with beneficial and safe therapeutic outcomes, which indicates the high potential of bionic nanomaterials in the treatment of tumors. Red blood cell membrane bionic nanosystems can be applied to heavy metal detoxification therapy as well as anti-tumor therapy.

Leukocyte Membrane in Bionic Nanomedicine

Leukocytes are blood cells responsible for repairing tissue damage, fighting off invaders, etc. They are part of the body’s specific and nonspecific immunity and are a very important line of defence. There are neutrophils, eosinophils, basophils, lymphocytes and mononuclear macrophages. It is precisely because of this immune capability that people have become fascinated by leukocyte membrane-encapsulated nanoparticles. The more closely studied leukocytes for bionic nanomedicine to date, though, are neutrophils and macrophages. Immune cells can’t be phagocytosed by the membrane of a macrophage – this can be overcome by self-recognition on the part of the cell; and neutrophils can be early in reaching inflammation or tumours via P/E selectins, P-selectin glycoprotein ligands, and integrins. In 2013, Alessandro et al. first described leukocyte membrane-encapsulated NPs. Leukocyte membrane-encapsulated NPs could circumvent phagocyte conditioning, delaying the mononuclear macrophage system’s infiltration, selectively binding to the site of inflammation, and encouraging the chemotherapeutic agent to transit through the endothelial cell, bypass the lysosomal pathway, accumulate more drugs in tumour tissue and extend nanomedicines’ time to reach their target.

Platelet Membrane in Bionic Nanomedicine

Platelets are little fragments of cytoplasmic material secreted from the cytoplasm of mature megakaryocytes in mammalian bone marrow. While platelets make up just between 0.5% and 1% of the total blood cells, they’re central to body hemostasis. Platelets will kick in the endogenous and exogenous coagulation mechanisms to coagulate blood vessels, convert fibrinogen to fibrin, and create clots with blood cells to close the wounding blood vessels and cause hemostasis. The platelet membranes are already bionic coatings that allow nanoparticles to bypass macrophage detection, catch on-target tumour cells and target inflammation sites, studies show recently.

Tumor Cell Membrane in Bionic Nanomedicine

Tumor cell membrane is produced after normal cells mutate. Recent studies have shown that tumor cells are ideal membrane coating materials. First, tumor cells have the ability to proliferate indefinitely and resist apoptosis, making it easier to collect and culture them when conducting bionic nanomedicine-related research experiments. Secondly, tumor cells are derived from normal cells and retain a variety of functional proteins, including membrane proteins that promote homologous binding (such as selectins and integrins), biomarkers involved in self-recognition and immune escape (such as CD47), and tumor antigens related to immune activation. They can escape the recognition and attack of the body’s immune system through a variety of mechanisms and be accurately transported to target organs or target tissues.

Other Cell Membranes in Bionic Nanomedicine

In line with the advent and advance of bionic nanomedicine, in addition to red blood cell membranes, white blood cell membranes, platelet membranes and tumour cell membranes, stem cell membranes, bacterial outer membrane vesicles etc. were also incorporated in drug delivery studies. Stem cells can self-replicate, multidirectionally differentiate and homing, and they are the primordial cells that build the human body’s tissues and organs. Cell membranes from stem cells are suitable for the transport of drugs because they’re immunegenic, they bypass macrophage phagocytosis, and they last a long time in the blood. When inflamed tissue secretes chemokines, adhesion molecules and growth factors, stem cells can hear them, and react by transferring to the injury area. Also promoting the homing of stem cell membranes is the relationship between surface receptors (CXCR and CD74) and cytokines released by cancerous or inflammatory tissue.

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