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The biomimetic strategy of using the cell membrane-coated nanoparticles can retain the physical and chemical properties of the nanoparticles and show the biological characteristics of the source cell membrane, which can further enhance the role of the nanodrug in tumor treatment. A hybrid cell membrane is the fusion of two or more different types of cell membranes. A hybrid cell membrane can endow nanoparticles with multiple biofunctions derived from the source cells compared with a single cell membrane. Hybrid cell membranes provide a foundation to stimulate extensive research into multifunctional biomimetic nano-drug delivery system (NDDS), which is expected to broaden the application of biomimetic nanotechnology in drug delivery systems. In this review paper, the types of hybrid cell membrane used to construct nano-drug delivery systems, the preparation and characterization methods, and cancer treatment research progress in recent years were reviewed.
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Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.
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Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.
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Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.
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Erythrocytes-camouflaged nanoparticles is an in vivo delivery system that uses erythrocytes or erythrocyte membrane nano vesicles as carriers for drugs, enzymes, peptides and antigens. This system has the advantages of good biocompatibility, long circulation cycle and efficient targeting. This review summarizes the type of carriers, their development history, the application of delivery strategies as well as their limitations and future challenges. Lastly, future directions and key issues in the development of this system are discussed.
Subject(s)
Pharmaceutical Preparations , Drug Delivery Systems , Vaccines , Erythrocytes , NanoparticlesABSTRACT
As an edible eukaryotic microorganism, Saccharomyces cerevisiae has the characteristics of high safety, rapid proliferation, low cost, easy transformation, etc. It has been widely used to produce vaccines, antibodies, insulin, etc. Up to now, yeast components, such as cell wall and yeast microcapsules, have been widely used in the treatment of tumors, inflammatory virus infection, post-traumatic osteoarthritis and other diseases. Among them, the components of yeast cell membrane are relatively simple and stable, which are easy to be extracted on a large scale. Therefore, yeast cell membrane material was used to construct yeast membrane vesicle nanosystem, and its biomedical application was preliminarily explored. In this study, Saccharomyces cerevisiae membrane vesicle (SMV) was prepared by co-extrusion method, and the particle size and surface potential of SMV, drug loading and release characteristics, stability, cell safety, and in vitro therapeutic effect were investigated. The results showed that the average particle size of SMV was 185.1 nm. Curcumin and silica nanoparticles were effectively encapsulated by co-incubation and ultrasonic methods, and the characteristics of cell membrane proteins were maintained. Moreover, SMV had good stability and biocompatibility. In addition, SMV could be effectively uptaken by macrophages RAW 264.7, and curcumin loaded SMV could effectively eliminate reactive oxygen species (ROS). In conclusion, the yeast plasma membrane vesicles prepared in this study could effectively deliver curcumin drugs and encapsulate nanoparticles, and could be effectively absorbed by macrophages and effectively eliminate ROS, providing new ideas and new methods for biomedical applications of yeast membrane materials.
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Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.
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In recent years ，biomimetic nanodelivery system based on cell membrane coating has developed rapidly and shows better biocompatibility and efficacy than traditional nanodelivery systems in a variety of diseases . Macrophages，as members of the immune system ，are closely related to the occurrence and development of a variety of diseases . Macrophages are derived from monocytes and can be polarized into M 1 and M 2 types after corresponding stimulation ： M1 macrophages involved in the proinflammatory reaction and M 2 macrophages involved in the inflammatory reaction . This paper reviews the application status of biomimetic nanoparticles coated with macrophage membrane in disease targeted therapy in recent years . Biomimetic nanoparticles coated with macrophage membrane has shown its high targeting and low immunogenicity in the treatment of malignant tumors （breast cancer ，colorectal cancer ，melanoma，glioma），Alzheimer’s disease ，liver ischemia -reperfusion injury ，atherosclerosis and so on . However，the research of Biomimetic nanoparticles coated with macrophage membrane currently focuses on anti -tumor research and is still in the laboratory research stage .
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Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
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Objective For the system of two single-walled carbon nanotubes (CNTs) placed in parallel onto a cell membrane, effects of the interaction between carbon nanotubes on wrapping manner of carbon tubes by the membrane were investigated, and the energy-optimized configurations were obtained. Methods A physical model for membrane-wrapped CNTs considering the interaction between two CNTs, and parameters describing the morphology of cell membrane and positions of CNTs were introduced. The Helfrich model based on continuum mechanics was used to calculate the membrane’s bending energy and the Lennard-Jones potential was introduced to describe the interaction between CNTs. Free energy of the system at different distances of NTs was calculated by the look-up table method, and the typical configurations of the membrane-wrapped CNTs was obtained. Results Compared with the case wherein the interaction between CNTs was not considered, the free energy profile of the system significantly changed. Deep well appeared on energy curve, when the distance between CNTs of carbon was 0.3 times of the tube diameter; as the distance between CNTs increased, the energy returned to the case wherein the interaction between CNTs was not considered. Conclusions With introduction of the interaction between CNTs, the wrapping manner of CNTs by the cell membrane changed, and the two CNTs tended to contact during their endocytosis. These results provide theoretical references for understanding and developing novel nanotube-based system for drug delivery.
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The development of nanotechnology has made it possible to develop safe, efficient, precise and controllable drug delivery system (DDS). Among them, organic or inorganic synthetic nanocarriers have been widely reported and used for the delivery of tumor therapeutic agents. However, some of carriers have several problems, such as easily eliminated by the body's immune system, difficult to preparation or poor safety in vivo. In recent years, with the development of biomedicine, biomimetic technology based biomembrane-mediated nanodrug delivery has organically integrated the low immunogenicity of natural biomembrane, cancer targeting, and the controllable and multifunctional of smart nanocarrier design. It will achieve a new breakthrough of nanotechnology in cancer targeted therapy. Based on the recent advances of cell membrane-derived biomimetic nanotechnology and the nanomedicine in the field of cancer therapy, this review discusses the three aspects including the experimental basis of cell membrane-derived biomimetic nanotechnology, the classification of biomimetic nanodrug delivery platforms, and the application in cancer targeted therapy. Therefore, the review will provide reference for the design of smart drug delivery system and its development in cancer targeted treatment.
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ObjectiveTo explore the effect of Buyang Huanwutang （BHD） on rehabilitation of ischemic stroke（IS） by cell membrane solid-phase chromatography and network pharmacology. MethodCell membrane solid-phase chromatography was performed to screen the specific binding components of BHD with hippocampal neurons. Targets of the specific components were retrieved based on PubChem and PharmMapper and those of IS were searched from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Then， the protein-protein interaction （PPI） network was constructed with STRING and Cytoscape 3.7.1， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the hub genes in the PPI network. Thereby， the mechanism of BHD in promoting IS rehabilitation was clarified. ResultA total of 13 specific components were identified. The hub genes were mainly involved in the biological processes of regulation of cell proliferation， protein phosphorylation， hypoxia response， and angiogenesis， and the pathways of Forkhead box O （FoxO） signaling pathway， adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） signaling pathway， nuclear factor kappa B （NF-κB） signaling pathway， and apoptosis pathway. ConclusionBHD may promote the recovery of IS by regulating FoxO， AMPK， NF-κB， and apoptosis pathways.
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Objective@#To investigate the mechanisms by which D-methionine (D-Met) eradicates Porphyromonas gingivalis biofilms by suppressing cyclic dimeric GMP (c-di-GMP) levels.@*Methods @#Cell viability, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were measured to determine the effective concentrations of D-Met, which were subsequently used in the following experiments. During the P. gingivalis biofilm formation inhibition experiment and the mature biofilm disassembly experiment, biofilm biomass, exopolysaccharide (EPS), biofilm morphology, integrity of the cell membrane, and the level of c-di-GMP were determined. @*Results @# D-Met < 40 mmol/L was biocompatible. During the biofilm formation inhibition and mature biofilm disassembly experiments, D-Met ≥ 20 mmol/L decreased the biofilm biomass and the production of EPS. SEM analysis showed that the extracellular matrix and bacterial density were drastically reduced by D-Met ≥ 20 mmol/L. TEM detection showed that 35 mmol/L D-Met ruptured the cell membrane during biofilm formation and increased the permeability of the cell membrane in the disassembly phase of mature biofilms. C-di-GMP levels decreased with increasing concentrations of D-Met in a concentration-dependent manner.@* Conclusion @# D-Met ≥ 20 mmol/L could eradicate P. gingivalis biofilms by suppressing c-di-GMP levels.
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OBJECTIVE To prepare and evalu ate doxorubicin-loaded red blood cell membrane chitosan-targeted nanoparticles of targeting tumor cell folate acid （FA）receptor（FA-RBC-DOX-CS-NPs）. METHODS Doxorubicin-loaded chitosan nanoparticles （DOX-CS-NPs） were prepared by ion cross-linking method. FA and amino polyethylene glycol phospholithin （NH2- PEG2000-DSPE）were covalently linked to modify the red blood cell membrane to construct FA-RBC-DOX-CS-NPS. FA-RBC- DOX-CS-NPs were characterized and investigated on in vitro drug release characteristics ，antitumor activity and endocytosis ability （investigation with human breast cancer MCF- 7 cells）. RESULTS Average particle size of FA-RBC-DOX-CS-NPs was （254.200± 2.651）nm，and polydispersity index was 0.199±0.031；Zeta potential was （－10.100±0.213）mV. FA-RBC-DOX-CS-NPs released fast in the tumor microenvironment （pH6.5）. Cellular experiments showed that ，the nanoparticles could inhibit the activity of MCF- 7 cell proliferation and improve the efficiency of endocytosis. CONCLUSIONS FA-RBC-DOX-CS-NPs are prepared successfully. The nanoparticles have good tumor cell targeting and endocytosis ability ，and can realize the enrichment of drugs in tumor cells.
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In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).
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Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane (CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol (PEG) was used to modifying magnetic graphene oxide (MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine (TCM). With this strategy, the constructed PEGylated MGO (PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of HeLa cell membrane (HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity (116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin, and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surface engineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.
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Objective:To explore the mechanism of rancidity during storage by researching the changes of water content， relative permeability of cell membrane and rancidity levels of Armeniacae Semen Amarum in deterioration process. Method:Armeniacae Semen Amarum samples under different storage conditions were evaluated and classified by sensory assessors， and samples with different levels of rancidity were obtained. Water content was measured by toluene method， and water activity was obtained by water activity meter. Malondialdehyde （MDA） and relative conductivity were measured using thiobarbituric acid colorimetry and conductivity meter， respectively. The content of fatty oil was obtained by Soxhlet extraction. The acid value and peroxide value were measured in accordance with the general rules 0713 and 2303 of the 2020 edition of <italic>Chinese Pharmacopoeia</italic> （part Ⅳ）， respectively. Based on the above experimental data， chemometric methods （cluster analysis， principal component analysis） were selected to establish classification and discriminant models of Armeniacae Semen Amarum with different rancidity levels， in order to verify the accuracy of the classification results. Result:According to the results of sensory evaluation， Armeniacae Semen Amarum samples were divided into three classes， including no rancidity， slight rancidity and rancidity. Compared with the no rancid samples， the color of surface and cotyledon were deepened in rancid samples， and the oil was appeared on surface with rancid taste. The values of water content， water activity， MDA content and relative conductivity were all significantly increased in deterioration process （<italic>P</italic><0.01）. The content of fatty oil was significantly decreased with the occurrence of rancidness （<italic>P</italic><0.01）， while the acid value and peroxide value increased significantly （<italic>P</italic><0.01）. The results of cluster analysis and principal component analysis showed that the rancid samples could be distinguished from the no rancid and slightly rancid samples. Conclusion:The storage conditions under high temperature and high humidity can accelerate the rancidness of Armeniacae Semen Amarum， which is accompanied by the increase of internal water content， the increase of cell membrane permeability and the occurrence of fatty acid rancidity. It is suggested that Armeniacae Semen Amarum should be stored in low temperature， dry environment， as well as short storage time.
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【Objective】 To explore the correlation between red blood cell lifespan and adhesion molecules on the surface of red blood cell membrane, in order to establish a method to detect the duration of red blood cell storage. 【Methods】 10 samples(10 mL each) of fresh red blood cell, collectedf rom 10 healthy voluntary blood donors, were divided into 5 age groups (layers) by Percoll density gradient centrifugation. The expression of CD47, CD44 and CD147 on the surface of red blood cell membrane in each layer was detected using flow cytometry. The variance of protein expression in each layer of red blood cells was analyzed by SPSS statistical software. 【Results】 The expression levels (%) of 3 adhesion molecules on the surface of red blood cell membranes from young to old were CD47: 14.44±2.61, 9.30±1.75, 7.84±1.49, 6.54±1.32 and 5.53±1.12 (P<0.01); CD44: 25.01±1.94, 19.22±1.52, 17.10±1.28, 15.18±1.11 and 13.56±1.08 (P<0.01); CD147: 33.46±1.99, 28.31±2.95, 23.83±1.59, 20.40±1.56 and 18.03±1.65 (P<0.01). 【Conclusion】 The expression levels of CD47, CD44 and CD147 on the surface of red blood cell membranes have showed a downward trend as the storage extended. These three protein adhesion molecules have showed a correlation with red blood cells lifespan, and could be used as detection markers of cell age.
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OBJECTIVE: To construct a biomimetic delivery system (U251/MSN-DOX), and assess its application of glioma targeted therapy. METHODS: U251 cell membrane was coated on the surface of mesoporous silica nanoparticles(MSN) by co-extrusion to prepare cell membrane biomimetic nanoparticles U251/MSN-DOX. The particle size, potential and morphology were characterized. The physical characteristics, loading content (LC) and encapsulation efficiency (EE) of these nanoparticles were determined. Their toxicity of normal cells was investigated. Their cellular uptake of different formulations in U251 was studied by flow cytometry and fluorescence confocal microscope. Additionally, we assessed the transmembrane transport efficiency of nanoparticles via in vitro BBB. RESULTS: The cell membrane-coated nanoparticles U251/MSN were spherical, and a distinct "core-shell" structure could be observed. The particle size was (135.70±3.85) nm, the LC was (18.57±2.17)%, and the EE was (64.99±2.52)%. The cell experiment showed that U251/MSN had low cytotoxicity and U251/MSN-DOX exhibited stronger cellular uptake ability and BBB transporting efficiency. CONCLUSION: The glioma cell membrane can be coated on the surface of MSN to construct biomimetic nanoparticles U251/MSN. The biomimetic nanoparticles not only are capable of targeting the homologous tumor cells, but also show the enhanced ability to penetrate BBB, which indicate potential applications in the field of tumor targeted drug delivery especially in brain tumor.
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OBJECTIVE: To investigate a biomimetic nano-targeted drug modifide by cancer cell membrane and to discuss its efficiency in breast cancer. METHODS: The lac-DOX/DOX was prepared by filming-rehydration method, and the 4T1 cell membrane was extracted at the same time. The lac-DOX /DOX@4T1m was prepared by sonication method.. The morphology of lac-DOX /DOX@4T1m was observed by a transmission electron microscopy. The protein on 4T1 cell membrane was analyzed by gel electrophoresis. The targeting of drugs to homologous cancer cells in vivo and in vitro were evaluated by cell uptake experiments and imaging experiments of small animals. 4T1 tumor-bearing Balb/c mice were built, the anti-tumor efficacy and biosafety of lac-DOX/ DOX@4t1m were evaluated. RESULTS: The prepared lac-DOX /DOX@4T1m have a regular spherical shape with an average particle diameter of (204.8±13.0)nm, and the protein entirety remained on the cell membrane. The results of cell uptake experiments and in vivo imaging experiments of mice showed that lac-DOX/DOX@4T1m can target 4T1 cells. Antitumor test results showed that lac-DOX/ DOX@4T1m could inhibit tumor growth more effectively and significantly reduce the damage to liver function. CONCLUSION: In this study, a bionic nano-drug is successfully prepared, which improve the tumor targeting and therapeutic effect, reduce the toxic effects of adriamycin, and improve the drug safety.