Cell Membrane-coated Nanoparticles Research Articles

Biomedical Applications of Cell Membrane‐Based Biomimetic Nano‐Delivery System

AbstractSurface modification of nanoparticles (NPs) is crucial for their effective utilization in diverse medical conditions, as it addresses challenges such as rapid passive clearance by the immune system, damage to the reticuloendothelial system, lack of specific cell targeting, and inadequate biocompatibility. The natural cell membrane (CM)‐coating technology has recently garnered considerable attention as an optimal strategy for enhancing artificial nanoformulations. This biomimetic technique directly confers inner NPs with multiple functions, such as immune evasion, precise targeting, and excellent biocompatibility, all of which are mediated by source cell‐inherent surface membrane proteins. Additionally, engineering techniques originally designed to enhance existing theranostic modalities employed in clinical settings are applied to natural CM carriers, thereby improving the physical properties of nanomaterials to drive further advancements. In this comprehensive review, diverse CM sources, such as red blood cells, platelets, white blood cells, cancer cells, bacteria, and other unconventional types, the core NPs employed in these cell membrane‐coated nanoparticles (CM‐NPs), preparation methods, and the latest advancements of CM‐NPs across diverse biomedical fields, are reviewed. Engineering strategies for enhancing natural CMs have also been emphasized. Furthermore, the review comprehensively addresses the major challenges and their corresponding solutions in the clinical translation of this evolving field.

Enhanced cancer immunotherapy through synergistic ferroptosis and immune checkpoint blockade using cell membrane-coated nanoparticles

BackgroundImmune checkpoint blockade (ICB) has achieved unprecedented success in inhibiting the progression and metastasis of many cancers. However, ICB regents as a single treatment have a relatively low overall response rate due to the tumor’s low immunogenicity and immunosuppressive microenvironment. Herein, we report a PD-1 cellular membrane-coated ferroptosis nanoinducer to potentiate cancer immunotherapy toward triple-negative breast cancer.ResultsThis study demonstrates that PD-1 membrane-coated RSL3 nanoparticles (PD-1@RSL3 NPs) have the ability to disrupt the PD-1/PD-L1 axis, leading to the activation of antitumor immunity in breast cancer. In addition, the nanoparticles promote the induction of tumor cell ferroptosis through GPX4 inhibition, enhanced infiltration of CD8+ T cells, and maturation of dendritic cells. The potentiated antitumor immune response induced by PD-1@RSL3 NPs significantly delayed tumor progression and extended the survival rate of mice with breast cancer xenografts.ConclusionsOur study suggest the potential of PD-1@RSL3 NPs as an effective therapeutic approach for breast cancer by promoting tumor cell ferroptosis and inducing antitumor immunity.

Genetically Engineered Cell Membrane-Coated Nanoparticles with High-Density Customized Membrane Receptor for High-Performance Drug Lead Discovery.

Cell membrane coating strategies have been increasingly researched due to their unique capabilities of biomimicry and biointerfacing, which can mimic the functionality of the original source cells in vivo but fail to provide customized nanoparticle surfaces with new or enhanced capabilities beyond natural cells. However, the field of drug lead discovery necessitates the acquisition of sufficient surface density of specific target membrane receptors, presenting a heightened demand for this technology. In this study, we developed a novel approach to fabricate high density of fibroblast growth factor receptor 4 (FGFR4) cell membrane-coated nanoparticles through covalent site-specific immobilization between genetically engineered FGFR4 with HaloTag anchor on cell membrane and chloroalkane-functionalized magnetic nanoparticles. This technique enables efficient screening of tyrosine kinase inhibitors from natural products. And the enhanced density of FGFR4 on the surface of nanoparticles were successfully confirmed by Western blot assay and confocal laser scanning microscopy. Further, the customized nanoparticles demonstrated exceptional sensitivity (limit of detection = 0.3 × 10-3 μg mL-1). Overall, the proposed design of a high density of membrane receptors, achieved through covalent site-specific immobilization with a HaloTag anchor, demonstrates a promising strategy for the development of cell membrane surface engineering. This approach highlights the potential of cell membrane coating technology for facilitating the advanced extraction of small molecules for drug discovery.

An anti-inflammatory Glyburide-loaded nanoghost for atherosclerosis therapy: A red blood cell based bio-mimetic strategy

Inflammation control is becoming a critical strategy for atherosclerosis management, because inflammation is involved in plaque progression. In this regard, a biomimetic strategy using cell membrane-coated nanoparticles has some promising advantages. In the study, a RBC membrane-based nanoghost containing Glyburide (Glibenclamide) was prepared using an extrusion method. The hydrodynamic size and zeta potential of the nanoghost were changed compared to PLGA nanoparticles. In addition, a nanoghost with a diameter and shell size of 125 nm and 8.3 nm was obtained based on the TEM measurement. The fabricated nanoghost was not only hemocompatible but also was biocompatible, showing no significant induction of apoptosis. According to RT-PCR assay, the expression levels of inflammatory genes including NLRP3, IL-1β, IL-18 caspase1, 8 and 9 were decreased. In accordance with in vitro anti-inflammation properties, total foam cells, total surface area in tunica intima and population of CD14+ cells were decreased in the rabbit model of atherosclerosis upon nanoghost treatment, compared to positive control. Furthermore, macrophages in aorta sections exhibited M1 to M2 polarization. In general, the development of Glyburide-loaded nanoghost can be considered as a potential therapeutic for controlling the progression and inflammation of atherosclerotic plaque.

A modular approach to enhancing cell membrane-coated nanoparticle functionality using genetic engineering.

Since their initial development, cell membrane-coated nanoparticles (CNPs) have become increasingly popular in the biomedical field. Despite their inherent versatility and ability to enable complex biological applications, there is considerable interest in augmenting the performance of CNPs through the introduction of additional functionalities. Here we demonstrate a genetic-engineering-based modular approach to CNP functionalization that can encompass a wide range of ligands onto the nanoparticle surface. The cell membrane coating is engineered to express a SpyCatcher membrane anchor that can readily form a covalent bond with any moiety modified with SpyTag. To demonstrate the broad utility of this technique, three unique targeted CNP formulations are generated using different classes of targeting ligands, including a designed ankyrin repeat protein, an affibody and a single-chain variable fragment. In vitro, the modified nanoparticles exhibit enhanced affinity towards cell lines overexpressing the cognate receptors for each ligand. When formulated with a chemotherapeutic payload, the modularly functionalized nanoparticles display strong targeting ability and growth suppression in a murine tumour xenograft model of ovarian cancer. Our data suggest genetic engineering offers a feasible approach for accelerating the development of multifunctional CNPs for a broad range of biomedical applications.

Supramolecularly Engineered Conjugate of Bacteria and Cell Membrane-Coated Magnetic Nanoparticles for Enhanced Ferroptosis and Immunotherapy of Tumors.

Although various ferroptosis inducers including magnetic nanoparticles (Fe3 O4 ) and iron-organic frameworks have been applied in cancer treatment, the mild immunogenicity, low targeting efficiency to the tumor, and poor tissue penetration have limited the therapeutic efficacy. Herein, a supramolecularly engineered conjugate between living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) and cancer cell membranes-coated Fe3 O4 nanoparticles is developed for improving targeted delivery of Fe3 O4 nanoparticles into the tumor tissue and for synergistic ferroptosis and immunotherapy of tumor. The enhanced ferroptosis induced by both Fe3 O4 nanoparticles and the loaded ferroptosis inducing agent (sulfasalazine (SAS)) effectively inhibits tumor growth and generates immune response via immunogenic cell death (ICD). The colonization of VNP in tumors also induces adaptive immune responses and further promotes ferroptosis. Fundamentally, the supramolecular conjugate of VNP and cell membranes-coated Fe3 O4 can potentiate the therapeutic capability of each other through mutually magnifying the ferroptosis and immunotherapy, resulting in significantly enhanced antitumor effects.

Targeted siRNA Delivery by Bioinspired Cancer Cell Membrane-Coated Nanoparticles with Enhanced Anti-Cancer Immunity.

Cell-membrane nanocarriers are usually constructed by modifying the nanoparticle surface with cell membrane extracts, which has a direct benefit in endowing targeting capacity to nanocarriers based on their original cell types. However, delivering nucleic acid cargos by cell membrane-based nanoparticles is difficult owing to the strong negative charge of the cell membrane fraction. In this study, we developed a cancer cell membrane-based drug delivery system, the cMDS, for efficient siRNA delivery. Meanwhile, the cancer-specific immune response stimulated by the gene vector itself could offer synergistic anti-cancer ability. The cMDS was prepared by ultrasound, and its transfection efficiency and anti-cancer ability were examined using cultures of CT26 cells. MTT and red blood cell hemolysis tests were performed to assess the safety of cMDS, while its targeted gene delivery and strong immune stimulation were investigated in a subcutaneous tumor model. Moreover, the detailed anti-cancer immune stimulation mechanisms of cMDS are uncovered by protein chip analysis. The cMDS was spherical core-shell structure. It showed high transfection efficiency and anti-cancer ability in vitro. In animal experiments, intravenously administered cMDS/siStat3 complex efficiently suppress the growth of colon cancer. Moreover, the result of protein chip analysis suggested that cMDS affect the migration and chemotaxis of immune cells. The cMDS shows obvious tumor tissue-specific accumulation properties and strong immune stimulation ability. It is an advanced targeted gene delivery system with potent immunotherapeutic properties.

Extending the In Vivo Residence Time of Macrophage Membrane-Coated Nanoparticles through Genetic Modification.

Nanoparticles coated with natural cell membranes have emerged as a promising class of biomimetic nanomedicine with significant clinical potential. Among them, macrophage membrane-coated nanoparticles hold particular appeal due to their versatility in drug delivery and biological neutralization applications. This study employs a genetic engineering approach to enhance their in vivo residence times, aiming to further improve their performance. Specifically, macrophages are engineered to express proline-alanine-serine (PAS) peptide chains, which provide additional protection against opsonization and phagocytosis. The resulting modified nanoparticles demonstrate prolonged residence times when administered intravenously or introduced intratracheally, surpassing those coated with the wild-type membrane. The longer residence times also contribute to enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in mouse models of lipopolysaccharide-induced lung injury and sublethal endotoxemia, respectively. This study underscores the effectiveness of genetic modification in extending the in vivo residence times of macrophage membrane-coated nanoparticles. This approach can be readily extended to modify other cell membrane-coated nanoparticles toward more favorable biomedical applications.

Cancer Cell Membrane-Coated Nanoparticle Co-loaded with Photosensitizer and Toll-like Receptor 7 Agonist for the Enhancement of Combined Tumor Immunotherapy.

Tumor immunotherapy has shown considerable therapeutic potential in the past few years, but the clinical response rate of immunotherapy is less than 20%. Encountering the high heterogeneity of tumors, it will be a general trend to apply combined therapy for cancer treatment. Photodynamic therapy (PDT) transiently kills tumor cells by producing reactive oxygen species (ROS), while residual tumor cells are prone to metastasis, leading to tumor recurrence. In combination with tumor immunotherapy, it is hoped to awaken the host immune system and eradicate residual tumor cells. Herein, cancer cell membrane-coated nanoparticles as a platform to combine PDT, TLR7 agonist, and tumor antigen for the enhancement of tumor therapeutic efficacy are designed. The final biomimetic nanoparticles (CCMV/LTNPs) can specifically kill tumor cells through PDT, while strong host antitumor immune responses are elicited to eliminate residue tumor cells under the help of immune adjuvant and tumor antigen from the cancer cell membrane. In summary, a photoimmunotherapy strategy is designed that synergistically enhances the tumor therapeutic effects by killing tumor cells through PDT and activating host antitumor immune responses through the co-delivery of adjuvant and tumor antigen, which may offer a promising strategy for clinical immunotherapy in the future.

Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms.

Targeting tumor-associated macrophages (TAMs) has emerged as a promising approach in cancer therapy. This article provides a comprehensive review of recent advancements in the field of nanomedicines targeting TAMs. According to the crucial role of TAMs in tumor progression, strategies to inhibit macrophage recruitment, suppress TAM survival, and transform TAM phenotypes are discussed as potential therapeutic avenues. To enhance the targeting capacity of nanomedicines, various approaches such as the use of ligands, immunoglobulins, and short peptides are explored. The utilization of live programmed macrophages, macrophage cell membrane-coated nanoparticles and macrophage-derived extracellular vesicles as drug delivery platforms is also highlighted, offering improved biocompatibility and prolonged circulation time. However, challenges remain in achieving precise targeting and controlled drug release. The heterogeneity of TAMs and the variability of surface markers pose hurdles in achieving specific recognition. Furthermore, the safety and clinical applicability of these nanomedicines requires further investigation. In conclusion, nanomedicines targeting TAMs hold great promise in cancer therapy, offering enhanced specificity and reduced side effects. Addressing the existing limitations and expanding our understanding of TAM biology will pave the way for the successful translation of these nano-therapies into clinical practice.

Antimicrobial effect of Streptococcus salivarius outer membrane-coated nanocomplexes against Candida albicans and oral candidiasis

Oral mucosal infection, especially oral candidiasis, is currently the most common oral mucosal disease. Traditional drug treatment regimens have difficulty adhering to mucous membranes, coupled with the unique anatomical and physiological characteristics of the oral cavity, thus reducing drug availability and limiting the effective time of drug action. Inspired by cell membrane-coated nanoparticles, this study aimed to construct a bionic adherent oral mucosal drug delivery system and investigated its therapeutic potential for oral candidiasis. The system was obtained by encapsulating Streptococcus salivarius K12 membranes on triclosan-loaded PLGA nanoparticles using an extrusion method. The constructed nanocomplexes (K12/TCS@PLGA-NPs) inherited the properties of the source cell membrane, bionically adhering to the oral mucosa and binding to the candida albicans hypha. Our in vitro and in vivo experiments have confirmed that K12/TCS@PLGA-NPs nanocomplexes significantly inhibits the formation of C. albicans biofilms and the development of oral candidiasis by enhancing the accumulation of drugs in lesions, optimizing drug efficacy. Furthermore, the biomimetic nanocomplexes could be considered safe and effective drug delivery systems, which hold considerable therapeutic promise for oral mucosal infections including candidiasis.

Recent Advances in Cell Membrane Coated-Nanoparticles as Drug Delivery Systems for Tackling Urological Diseases.

Recent studies have revealed the functional roles of cell membrane coated-nanoparticles (CMNPs) in tackling urological diseases, including cancers, inflammation, and acute kidney injury. Cells are a fundamental part of pathology to regulate nearly all urological diseases, and, therefore, naturally derived cell membranes inherit the functional role to enhance the biopharmaceutical performance of their encapsulated nanoparticles on drug delivery. In this review, methods for CMNP synthesis and surface engineering are summarized. The application of different types of CMNPs for tackling urological diseases is updated, including cancer cell membrane, stem cell membrane, immune cell membrane, erythrocytes cell membranes, and extracellular vesicles, and their potential for clinical use is discussed.

Cell membrane-coated nanoparticles for cancer therapy

<p style="text-align: justify;">Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.</p>

Cell membrane-coated nanoparticles for cancer therapy

<p>Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.</p>

Mesenchymal Stem Cell Membrane-Coated TPCS2a-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy.

Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS2a). TPCS2a@NPs of 98.89 ± 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 ± 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS2a@NPs, size of 139.31 ± 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS2a@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS2a@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS2a in mMSC-TPCS2a@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen (1O2) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC50 < 0.15 µM) and three-dimensional spheroids.

Cell membrane-coated nanomaterials for cancer therapy.

With the development of nanotechnology, nanoparticles have emerged as a delivery carrier for tumor drug therapy, which can improve the therapeutic effect by increasing the stability and solubility and prolonging the half-life of drugs. However, nanoparticles are foreign substances for humans, are easily cleared by the immune system, are less targeted to tumors, and may even be toxic to the body. As a natural biological material, cell membranes have unique biological properties, such as good biocompatibility, strong targeting ability, the ability to evade immune surveillance, and high drug-carrying capacity. In this article, we review cell membrane-coated nanoparticles (CMNPs) and their applications to tumor therapy. First, we briefly describe CMNP characteristics and applications. Second, we present the characteristics and advantages of different cell membranes as well as nanoparticles, provide a brief description of the process of CMNPs, discuss the current status of their application to tumor therapy, summarize their shortcomings for use in cancer therapy, and propose future research directions. This review summarizes the research progress on CMNPs in cancer therapy in recent years and assesses remaining problems, providing scholars with new ideas for future research on CMNPs in tumor therapy.

Cell membrane-coated nanoparticles for the treatment of cancer.

Cell membrane-coated nanoparticles for the treatment of cancer.

Interleukin-10-alveolar macrophage cell membrane-coated nanoparticles alleviate airway inflammation and regulate Th17/regulatory T cell balance in a mouse model.

Allergic airway disease (AAD) is a chronic disease characterized by airway inflammation, bronchoconstriction, and hyperresponsiveness. Although exogenous interleukin-10 (IL-10) alleviates allergic inflammation, it has a short half-life in vivo. Cell membrane-coated nanomaterials have been shown to protect therapeutic payloads and increase therapeutic efficacy. This study was aimed at investigating the efficacy of a novel macrophage-based nanoparticle drug for the treatment of house dust mite (HDM)-induced allergic airway diseases. IL-10-poly (lactic-co-glycolic acid (PLGA) nanoparticles were encapsulated in alveolar macrophage cell membranes. An allergic airway disease mouse model was established by repeated inhalation of HDM extracts. The mice were treated with free IL-10, IL-10-PLGA nanoparticles (IL10-NP), or IL-10-alveolar macrophage cell membrane-coated nanoparticles (IL10-AMNP). The therapeutic effects were evaluated by measuring airway hyperresponsiveness, lung inflammation, cytokine levels, and regulatory T cells (Treg)- T-helper 17 (Th17) cell balance. Compared to free IL-10, IL10-AMNP significantly reduced airway hyperresponsiveness and T-helper 2 (Th2)/Th17 cytokines and inhibited neutrophilia and eosinophilia recruitment into the airways of HDM-induced mouse models. Additionally, the balance between Tregs and Th17 cells was significantly improved in groups treated with IL10-AMNP. This study demonstrated that PLGA nanoparticle cores coated with alveolar macrophage cell membranes can effectively deliver therapeutic cytokines to the lungs and improve the homeostatic balance between Tregs and Th17 cells. These findings suggest that macrophage-based nanoparticle drugs represent a promising approach for treating allergic airway diseases.

Cell membrane camouflaged mesoporous bioactive glass nanoparticles embedding glucose oxidase for enhancing targeted anti-tumor catalytic therapy

Breast cancer has emerged as the most diagnosed common cancer, accounting for approximately 11.7% of all cases globally, and is a considerable threat to human health. The construction of a nano-drug delivery system highly relevant to the clinically real world is a timeless and urgent matter. Here, we present an intelligent bioinspired nano-platform based on mesoporous bioactive glass nanoparticles (MBG NPs) combined with cell membrane camouflage and enzyme-catalyzed killing to suppress in situ breast cancer. M0 phenotype macrophages were identified as possessing a specific high infiltration fraction in breast cancer patients using TCGA analysis and were consequently selected as cell membrane-derived donors. Subsequently, the macrophage-coated MBG NPs exhibited superior evasion of clearance by myeloid lineage cells (monocytes, neutrophils, and dendritic cells) and favorable targeting properties to breast cancer tumors compared to cell membrane-free and breast cancer cell membrane-coated nanoparticles. The macrophage membrane-camouflaged MBG NPs were then applied to load the glucose oxidase (GOx), followed by catalyzing glucose to trigger intense oxidative stress and death of breast cancer cells, thereby inhibiting tumor progression. Additionally, the macrophage membrane camouflaged MBG embedding glucose oxidase delivery system effectively overcomes the dramatic changes in hematological and biochemical parameters with non-specific glucose catalysis, conceivably minimizing the risk of toxicity. Taken together, our findings pave the way for constructing an intelligent biomimetic MBG nano-loading enzyme platform suitable for targeted breast cancer therapy.

Cell membrane-coated nanoparticles: An emerging antibacterial platform for pathogens of food animals.

Bacterial pathogens of animals impact food production and human health globally. Food animals act as the major host reservoirs for pathogenic bacteria and thus are highly prone to suffer from several endemic infections such as pneumonia, sepsis, mastitis, and diarrhea, imposing a major health and economical loss. Moreover, the consumption of food products of infected animals is the main route by which human beings are exposed to zoonotic bacteria. Thus, there is excessive and undue administration of antibiotics to fight these virulent causative agents of food-borne illness, leading to emergence of resistant strains. Thus, highprevalence antibiotic-resistant resistant food-borne bacterial infections motivated the researchers to discover new alternative therapeutic strategies to eradicate resistant bacterial strains. One of the successful therapeutic approach for the treatment of animal infections, is the application of cell membrane-coated nanoparticles. Cell membranes of several different types of cells including platelets, red blood cells, neutrophils, cancer cells, and bacteria are being wrapped over the nanoparticles to prepare biocompatible nanoformulations. This diversity of cell membrane selection and together with the possibility of combining with an extensive range of nanoparticles, has opened a new opportunistic window for the development of more potentially effective, safe, and immune evading nanoformulations, as compared to conventionally used bare nanoparticle. This article will elaborately discuss the discovery and development of novel bioinspired cell membrane-coated nanoformulations against several pathogenic bacteria of food animals such as Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Salmonella enteritidis, Campylobacter jejuni, Helicobacter pylori, and Group A Streptococcus and Group B Streptococcus.