Cell Membrane-coated Nanoparticles Research Articles

Exocytosis blockade of endoplasmic reticulum-targeted nanoparticle enhances immunotherapy

Current endoplasmic reticulum (ER)-targeted strategies remain unsatisfactory, largely owing to limited ER accumulation and rapid exocytosis of nanodrugs after their ER arrival. Herein, we propose a brand-new ER-targeting strategy and demonstrate its underlying mechanism: (1) homologous cancer cell membrane-coated nanoparticle (HCC@NP) circumvents lysosome degradation via caveolae-related endocytosis and preferentially accumulates in ER-Golgi network due to the SNARE proteins existing on the surface of HCC@NP, allowing the recognition and binding of HCC@NP to ER-Golgi network; (2) loaded Brefeldin (BFA) is directed to its action site and block HCC@NP exocytosis from ER via coat protein type I (COPI) vesicle transport inhibition, achieving high-efficiency and long-term ER retention. This sequentially engaging and blocking ER-associated pathway approach induces potent ER stress-associated immunogenic cell death (ICD) events and recruits CD8+ T cells. Combination with anti-PD-L1 therapy overcomes adaptive PD-L1 enrichment following ICD induction. The rationally designed platform shows significant in vivo therapeutic efficacy by promoting anti-tumor immunity and reversing immunosuppression.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer

BackgroundMono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.ResultsPoly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells”-based cocktail therapy.Conclusion“Nano-targeted cells”-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.Graphical

Acute myeloid leukemia cell membrane-coated nanoparticles for cancer vaccination immunotherapy

Cancer vaccines are promising treatments to prevent relapse after chemotherapy in acute myeloid leukemia (AML) patients, particularly for those who cannot tolerate intensive consolidation therapies. Here, we report the development of an AML cell membrane-coated nanoparticle (AMCNP) vaccine platform, in which immune-stimulatory adjuvant-loaded nanoparticles are coated with leukemic cell membrane material. This AMCNP vaccination strategy stimulates leukemia-specific immune responses by co-delivering membrane-associated antigens along with adjuvants to antigen-presenting cells. To demonstrate that this AMCNP vaccine enhances leukemia-specific antigen presentation and T cell responses, we modified a murine AML cell line to express membrane-bound chicken ovalbumin as a model antigen. AMCNPs were efficiently acquired by antigen-presenting cells in vitro and in vivo and stimulated antigen cross-presentation. Vaccination with AMCNPs significantly enhanced antigen-specific T cell expansion and effector function compared with control vaccines. Prophylactic vaccination with AMCNPs enhanced cellular immunity and protected against AML challenge. Moreover, in an AML post-remission vaccination model, AMCNP vaccination significantly enhanced survival in comparison to vaccination with whole leukemia cell lysates. Collectively, AMCNPs retained AML-specific antigens, elicited enhanced antigen-specific immune responses, and provided therapeutic benefit against AML challenge.

Virus-Mimicking Cell Membrane-Coated Nanoparticles for Cytosolic Delivery of mRNA.

Effective endosomal escape after cellular uptake represents a major challenge in the field of nanodelivery, as the majority of drug payloads must localize to subcellular compartments other than the endosomes in order to exert activity. In nature, viruses can readily deliver their genetic material to the cytosol of host cells by triggering membrane fusion after endocytosis. For the influenza A virus, the hemagglutinin (HA) protein found on its surface fuses the viral envelope with the surrounding membrane at endosomal pH values. Biomimetic nanoparticles capable of endosomal escape were fabricated using a membrane coating derived from cells engineered to express HA on their surface. When evaluated in vitro, these virus-mimicking nanoparticles were able to deliver an mRNA payload to the cytosolic compartment of target cells, resulting in the successful expression of the encoded protein. When the mRNA-loaded nanoparticles were administered in vivo, protein expression levels were significantly increased in both local and systemic delivery scenarios. We therefore conclude that utilizing genetic engineering approaches to express viral fusion proteins on the surface of cell membrane-coated nanoparticles is a viable strategy for modulating the intracellular localization of encapsulated cargoes.

Neural Cell Membrane-Coated Nanoparticles for Targeted and Enhanced Uptake by Central Nervous System Cells.

Targeted drug delivery to specific neural cells within the central nervous system (CNS) plays important roles in treating neurological disorders, such as neurodegenerative (e.g., targeting neurons) and demyelinating diseases [e.g., targeting oligodendrocytes (OLs)]. However, the presence of many other cell types within the CNS, such as microglial and astrocytes, may lead to nonspecific uptake and subsequent side effects. As such, exploring an effective and targeted drug delivery system is of great necessity. Synthetic micro-/nanoparticles that have been coated with biologically derived cellular membranes have emerged as a new class of drug delivery vehicles. However, the use of neural cell-derived membrane coatings remains unexplored. Here, we utilized this technique and demonstrated the efficacy of targeted delivery by using four types of cell membranes that were derived from the CNS, namely, microglial, astrocytes, oligodendrocyte progenitor cells (OPCs), and cortical neurons. A successful cell membrane coating over poly(ε-caprolactone) nanoparticles (NPs) was confirmed using dynamic light scattering, zeta potential measurements, and transmission electron microscopy. Subsequently, an extensive screening of these cell membrane-coated NPs was carried out on various CNS cells. Results suggested that microglial and OLs were the most sensitive cell types toward cell membrane-coated NPs. Specifically, cell membrane-coated NPs significantly enhanced the uptake efficiency of OLs (p < 0.001). Additionally, a temporal uptake study indicated that the OLs took up microglial membrane-coated NPs (DPP-PCL-M Mem) most efficiently. Besides that, coating the NPs with four types of the CNS cell membrane did not result in obvious specific uptake in microglial but reduced the activation of microglial, especially for DPP-PCL-M Mem (p < 0.01). Taken together, DPP-PCL-M Mem were uptaken most efficiently in OLs and did not induce significant microglial activation and may be most suitable for CNS drug delivery applications.

Cell membrane-coated nanoparticles as peroxidase mimetics for cancer cell targeted detection and therapy

The development of novel and efficient recognition molecules that can be easily modified by nanomaterials to achieve ultra-sensitive and specific cancer cell analysis is of great significance for its early diagnosis and timely prognosis. Herin, a new nanostructured hybrid based on cell membrane-coated Au cores− ultrathin Pt skins composite nanoparticles (Au@Pt@CM NPs) were developed for in vitro detection and treatment of cancer cells. In this strategy, the Au@Pt NPs acted as the signal transducer, and the cell membrane were used as the cancer-cell recognition tool. The synthesized Au@Pt@CM NPs could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of the hydrogen peroxide and were demonstrated to have excellent peroxidase-like activity. Coated with the source cancer cell membrane, the nanoparticles achieved highly specific self-recognition to the source cell. Therefore, the colorimetric method based on Au@Pt@CM NPs could detect the cancer cells in the linear range from 50 to 100000 cells/mL with a limit of detection of 5 cells/mL, which is much lower than other colorimetric detection methods. Afterwards, the nanoparticles as a mimetic enzyme were used for therapeutics of cancer cells through the ROS-mediated oxidative damage. Due to the change of the redox state in the cells by the Au@Pt@CM NPs, the hybrid can achieve the growth inhibitory effect and the selective killing effect on cancer cells. It can be expected that this novel hybrid membrane coating method will bring new insight into developing targeted nanomaterials for tumor treatment and detection.

Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications.

The biomedical field is currently reaping the benefits of research on biomimetic nanoparticles (NPs), which are synthetic nanoparticles fabricated with natural cellular materials for nature-inspired biomedical applications. These camouflage NPs are capable of retaining not only the physiochemical properties of synthetic nanoparticles but also the original biological functions of the cellular materials. Accordingly, NPs coated with cell-derived membrane components have achieved remarkable growth as prospective biomedical materials. Particularly, bacterial outer membrane vesicle (OMV), which is a cell membrane coating material for NPs, is regarded as an important molecule that can be employed in several biomedical applications, including immune response activation, cancer therapeutics, and treatment for bacterial infections with photothermal activity. The currently available cell membrane-coated NPs are summarized in this review. Furthermore, the general features of bacterial OMVs and several multifunctional NPs that could serve as inner core materials in the coating strategy are presented, and several methods that can be used to prepare OMV-coated NPs (OMV-NPs) and their characterization are highlighted. Finally, some perspectives of OMV-NPs in various biomedical applications for future potential breakthrough are discussed. This in-depth review, which includes potential challenges, will encourage researchers to fabricate innovative and improvised, new-generation biomimetic materials through future biomedical applications.

Cell membrane-coated nanoparticles for immunotherapy

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and enhancing disease-targeting efficiency of nanoparticles, membrane coating nanotechnology exhibits great potential in the disease diagnosis and therapeutics due to both the structural and functional preservation of membrane proteins from source cells. Benefiting the inherited immune-regulation capacities, this review mainly summarized the latest development of such biomimetic nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases. This review mainly summarized the latest development of cell membrane-coated nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases.

Nanoparticle approaches against SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure–function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.

Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition.

Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles (“cellular nanosponges”) mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.

Biomimetic immunomodulation by crosstalk with nanoparticulate regulatory T cells

<h2>Summary</h2> Hyperactive immunity mediates the development and progression of various immuno-inflammatory diseases. However, the use of immunosuppressive or anti-inflammatory agents has been largely restricted either by off-target side effects or by individual interaction site. Here, we describe a biomimetic manipulation strategy for immunosuppression by crosstalk with regulatory T (Treg) cell membrane-coated nanoparticles. Due to the reservation of intrinsic membrane proteins and function from Treg cells, coated nanoparticles can directly interact with multifaceted overactive immune cells. By virtue of this unique characteristic, nanoparticulate Treg cells inhibit macrophage-osteoclast differentiation, the maturation of dendritic cells, and the activation of effector T cells. In both murine and canine models of periodontitis, these nanoparticles successfully suppress excessive immune responses, alleviating inflammation and curbing alveolar bone resorption. Our work reveals how dysregulated immune responses can be effectively manipulated by biomimetic immunomodulation and proposes the utilization of nanoparticulate Treg cells as a promising approach to treat immuno-inflammatory diseases.

Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma

ObjectiveThe emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect.MethodsThe degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the PEG-TE10@PLGA@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The In vitro homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the in vitro anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect in vivo and the bio-safety of PMPNs.ResultsThe prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety.ConclusionIn this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

Retraction of "Red Blood Cell Membrane-Coated Silica Nanoparticles Codelivering DOX and ICG for Effective Lung Cancer Therapy".

[This retracts the article DOI: 10.1021/acsomega.0c01541.].

Inside-Out-Oriented Cell Membrane Biomimetic Magnetic Nanoparticles for High-Performance Drug Lead Discovery.

Biomimetic cell membrane-coated nanoparticles have been broadly applied because of their superior biochemical properties. The right-side-out cell membrane coating manner provides nanoparticles with an immune-evasive stealth function in vivo. However, this acts as a drag for drug discovery when the drug targets are the intracellular domain of transmembrane receptors. Herein, inside-out-oriented cell membrane-coated nanoparticles were prepared for screening tyrosine kinase inhibitors, which specifically interacted with the intracellular kinase domain of the epidermal growth factor receptor. Biotinylated human lung adenocarcinoma epithelial cell membranes specifically interacted with streptavidin-immobilized Fe3O4 magnetic nanoparticles and then formed inside-out-oriented cell membrane-coated magnetic nanoparticles (IOCMMNPs). The cell membrane orientation of the IOCMMNPs was successfully confirmed by immunogold electron microscopy, fluorescently labeled confocal microscopy, sialic acid quantification assay, and the adsorption capacity assay. Moreover, IOCMMNPs possessed satisfactory binding capacity, selectivity, and high sensitivity (limit of detection = 0.4 × 10-3 μg mL-1). Ultimately, IOCMMNPs successfully targeted two main compounds from Strychnos nux-vomica whose potential antitumor activities were further validated by pharmacological studies. The application of the inside-out cell membrane coating strategy further enhances the drug screening efficiency and broadens the insight and methodologies for drug lead discovery. This inside-out cell membrane coating concept also provides a method for the future development of engineered cell membrane-coated nanotechnology.

A Polymer Multicellular Nanoengager for Synergistic NIR-II Photothermal Immunotherapy.

Cell-membrane-coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second-near-infrared-window (NIR-II) photothermal immunotherapy is reported. The nanoengager consists of an NIR-II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross-interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor-cell-coated nanoparticles. Upon deep-tissue penetrating NIR-II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti-tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell-membrane-coating approach to develop photo-immunotherapeutic agents for cancer therapy.

Immune Cell Membrane-Coated Biomimetic Nanoparticles for Targeted Cancer Therapy.

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.

CD4+ T cell-mimicking nanoparticles encapsulating DIABLO/SMAC mimetics broadly neutralize HIV-1 and selectively kill HIV-1-infected cells.

HIV-1 is a major global health challenge. The development of an effective vaccine and a therapeutic cure are top priorities. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 stymies this progress. Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable.Methods: We investigated the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) encapsulating the DIABLO/SMAC mimetics LCL-161 or AT-406 (also known as SM-406 or Debio 1143) to both neutralize HIV-1 and selectively kill HIV-1-infected resting CD4+ T cells and macrophages.Results: DIABLO/SMAC mimetic-loaded TNP displayed outstanding neutralizing breadth and potency, and selectively kill HIV-1-infected cells via autophagy-dependent apoptosis while having no drug-induced off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect.Conclusion: DIABLO/SMAC mimetic loaded TNP have the potential to be used as therapeutic agents to neutralize cell-free HIV-1 and to kill specifically HIV-1-infected cells as part of an HIV-1 cure strategy.

An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection.

The cell membrane-coated nanoparticles (MNPs) showed great potential in treating infectious disease due to their superior biofunctions in improving biocompatibility of nanoparticles and neutralization of pathogen or toxins. However, bone infection is accompanied with severe inflammation and bone loss, which also requires anti-inflammatory and osteoconductive treatment. The conventional membrane coating method has to undergo ultrasonication and extrusion procedures, which reduces the functionality of cell membrane and limits the choice of nanoparticles. In this study, we proposed an electroporation-based membrane coating strategy to facilitate the synthesis of MNPs to tackle those problems.Methods: Magnetic composite nanoparticles with osteoconductive Ca3(PO4)2 and bactericidal TiO2 were assembled into macrophages through phagocytosis and then collected to expose in electric field for obtaining macrophage membrane-coating nanoparticles. By using molecular dynamics simulation and materials characterizations, the cell membrane coating efficiency was confirmed. The in vitro anti-bacterial and anti-inflammatory abilities were tested by bacteria culturing and immune cells activation. Then drug-resistant bacteria induced bone infection model was established to verify its in vivo therapeutic effects.Results: The coated membrane prepared through electroporation reserved the integrality of membrane structure and right-sidedness, with more functional proteins. Those led to the superior properties of recognition and adsorption with bacteria, toxins and inflammatory cytokines. Owing to the benefits of electroporation, the MNPs exhibited significant better antibacterial and anti-inflammatory abilities for enhancing the tissue repair process.Conclusion: This study provides a novel self-assembly cell membrane coating strategy by electroporation to construct multifunctional membrane-coating nanoparticles for bone infection treatment. This strategy not only improves the functions of coated membrane, but is also proved to be universal for varies nanoparticles or cells, indicating a great potential for future applications in the bioengineering field.

Hybrid-cell membrane-coated nanocomplex-loaded chikusetsusaponin IVa methyl ester for a combinational therapy against breast cancer assisted by Ce6.

Breast cancer is the most common cancer in women and occurs mostly with poor outcomes. Our objective was to endow synthetic lethality to the phytoconstituent chikusetsusaponin IVa methyl ester (CSME, S), a special phytoconstituent from traditional Chinese medicine (TCM), Panax japonicus, with the photodynamic agent chlorin e6 (Ce6, C) and enhance the therapeutic efficacy against breast cancer using cell membrane-coated liposome nanoparticles (liposome, L). The delivery system based on liposomes was camouflaged by a hybrid cell membrane (RBC membrane and cancer cell membrane, M) and RGD (R) surface modifications to improve the solubility, targeting and treatment outcomes of CSME. Our results showed the successful development of nanocomplexes with extended half-life, increased immune evasion and targeted ability at the tumor site and good antitumor activity without side effects to normal tissue. The anti-tumor mechanism of nanocomplexes is related to cell proliferation regulation and apoptosis induction. Overall, this drug-delivery system provides a good alternative for breast cancer therapy using a natural active phytoconstituent.