Cell Membrane-coated Nanoparticles Research Articles

Cell Membrane-Coated Nanoparticles for Precision Medicine: A Comprehensive Review of Coating Techniques for Tissue-Specific Therapeutics.

Nanoencapsulation has become a recent advancement in drug delivery, enhancing stability, bioavailability, and enabling controlled, targeted substance delivery to specific cells or tissues. However, traditional nanoparticle delivery faces challenges such as a short circulation time and immune recognition. To tackle these issues, cell membrane-coated nanoparticles have been suggested as a practical alternative. The production process involves three main stages: cell lysis and membrane fragmentation, membrane isolation, and nanoparticle coating. Cell membranes are typically fragmented using hypotonic lysis with homogenization or sonication. Subsequent membrane fragments are isolated through multiple centrifugation steps. Coating nanoparticles can be achieved through extrusion, sonication, or a combination of both methods. Notably, this analysis reveals the absence of a universally applicable method for nanoparticle coating, as the three stages differ significantly in their procedures. This review explores current developments and approaches to cell membrane-coated nanoparticles, highlighting their potential as an effective alternative for targeted drug delivery and various therapeutic applications.

Cancer Cell Membrane-Biomimetic Nanoparticles Based on Gelatin and Mitoxantrone for Synergetic Chemo-Photothermal Therapy of Metastatic Breast Cancer.

The purpose of this paper is to develop a cancer cell membrane biomimetic nanodrug delivery system (NDDS) to achieve an enhanced chemo-photothermal synergistic antitumor effect. The biomimetic NDDSs are composed of mitoxantrone (MIT)-loaded gelatin nanoparticles and IR820-encapsulated 4T1 cancer cell membrane-derived vesicles. The biomimetic NDDS displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved 4T1 cell uptake through homologous targeting and effectively reduced internalization of macrophages. In vivo photothermal imaging results further showed that the NDDS could be enriched at the tumor site for 48 h and could raise the temperature of the tumor area to 60 °C within 5 min under 808 nm laser irradiation. Finally, NDDS successfully inhibited primary tumor growth (over 89% inhibition) and significantly inhibited lung metastasis. This study may provide a new strategy for personalized chemotherapy-photothermal combination therapy of metastatic breast cancer using tumor cell membranes from cancer patients as drug carriers.

SARS-CoV-2 Neutralization by Cell Membrane-Coated Antifouling Nanoparticles.

The global outbreak of the COVID-19 pandemic has indisputably wreaked havoc on societies worldwide, compelling the scientific community to seek urgently needed therapeutic agents with low-cost and low-side effect profiles. Numerous approaches have been investigated in the quest to prevent or treat COVID-19, but many of them exhibit unwelcome side effects, such as dysfunctional viral immune responses and inflammation. Herein, we present the preparation of solid natural human pulmonary alveolar epithelial cell (ATII) membrane-coated PLGA NPs (PLGA NPs@ATII-M), which demonstrate remarkable affinity and competitiveness to neutralize the SARS-CoV-2 S1 protein-coated NPs (SCMMA NPs-S1), which are employed as a surrogate for coronavirus particles. In addition, we first considered the antifouling properties of these types of NPs, and we found that this membrane-coated NP formulation boasts excellent antifouling capabilities, which serve to protect their neutralization properties out of shielding by protein coronas in blood circulation. Moreover, this formulation is easily prepared and stored with a low-cost profile and exhibits good specificity, high targeting efficiency, and potentially side effect avoiding, thus making it a highly promising candidate for COVID-19 treatment.

Hybrid Cell Membrane‐Coated Nanoparticles for Biomedical Applications

There is growing interest in developing cell membrane‐coated nanoparticles (CNPs) for unique host cell mimicry and therapeutic applications. The continuous evolution of this technology has motivated the coating of nanoparticles with hybrid membranes originating from diverse cell types. The resulting hybrid cell membrane‐coated nanoparticles (hybrid CNPs) exhibit a higher level of synergy among multifunctionalities with better multitasking capabilities than their monotypic membrane‐coated counterparts. This advancement has catalyzed the initiation of numerous research opportunities, marking the advent of a promising frontier in therapeutic applications. This review outlines emerging biomedical applications of hybrid CNPs, focusing on drug targeting, immune modulation, biological neutralization, and disease diagnosis. Within each application, the review underscores how the strategic hybridization of distinct cell membranes augments the resulting nanoparticle therapeutic efficacy. Overall, the insights presented herein consolidate our understanding of current applications and may inspire novel designs with new biomedical applications.

Cell Membrane-Coated Nanoparticles for Dental, Oral, and Craniofacial Diseases.

Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment. These nanoparticles have demonstrated substantial advantages in drug targeting, prolonging blood circulation time, penetrating biofilms, and immune escape. With the assistance of CMCNPs, the therapeutic effects of dental, oral, and craniofacial diseases can reach a higher level. CMCNPs have been applied for dental, oral, and craniofacial diseases for various conditions such as head and neck cancer, periodontal disease, and oral biosignal detection. For the therapies of head and neck cancer, CMCNPs have been widely utilized as a tool of chemotherapy, phototherapy, and immunotherapy, while yet to be exploited in imaging technique. In the end, we summarized the challenges and prospectives of CMCNPs for dental, oral, and craniofacial diseases: large-scale production with uniform standards and high quantity, extensive application directions in dental, oral, and craniofacial regions (implant, endodontics), and the promotion of its clinical application.

Cell membrane coated nanoparticles as a biomimetic drug delivery platform for enhancing cancer immunotherapy.

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede the growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical cancer therapy, the resistance of cancer cells to immunotherapeutic medications and other apprehensions impede the attainment of sustained advantages for most patients. Recent advancements in nanotechnology for drug delivery hold promise in augmenting the efficacy of immunotherapy. However, the efficacy is currently constrained by the inadequate specificity of delivery, low rate of response, and the intricate immunosuppressive tumor microenvironment. In this context, the investigation of cell membrane coated nanoparticles (CMNPs) has revealed their ability to perform targeted delivery, immune evasion, controlled release, and immunomodulation. By combining the advantageous features of natural cell membranes and nanoparticles, CMNPs have demonstrated their unique potential in the realm of cancer immunotherapy. This review aims to emphasize recent research progress and elucidate the underlying mechanisms of CMNPs as an innovative drug delivery platform for enhancing cancer immunotherapy. Additionally, it provides a comprehensive overview of the current immunotherapeutic strategies involving different cell membrane types of CMNPs, with the intention of further exploration and optimization.

Cell membrane coated nanoparticles: cutting-edge drug delivery systems for osteoporosis therapy.

Osteoporosis, characterized by a reduction in bone mineral density, represents a prevalent skeletal disorder with substantial global health implications. Conventional therapeutic strategies, exemplified by bisphosphonates and hormone replacement regimens, though effective, encounter inherent limitations and challenges. Recent years have witnessed the surge of cell-membrane-coated nanoparticles (CMNPs) as a promising intervention for osteoporosis, leveraging their distinct attributes including refined biocompatibility, heightened pharmaceutical payload capacity, as well as targeted drug release kinetics. However, a comprehensive review consolidating the application of CMNPs-based therapy for osteoporosis remains absent within the existing literature. In this review, we provide a concise overview of the distinctive pathogenesis associated with osteoporosis, alongside an in-depth exploration of the physicochemical attributes intrinsic to CMNPs derived from varied cellular sources. Subsequently, we explore the potential utility of CMNPs, elucidating emerging trends in their deployment for osteoporosis treatment through multifaceted therapeutic approaches. By linking the notable attributes of CMNPs with their roles in mitigating osteoporosis, this review serves as a catalyst for further advances in the design of advanced CMNPs tailored for osteoporosis management. Ultimately, such progress is promising for enhancing outcomes in anti-bone loss interventions, paving the way for clinical translation in the near future.

Cell membrane-coated biomimetic nanomedicines: productive cancer theranostic tools.

As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research.

Advances in biomimetic nanomaterial delivery systems: harnessing nature's inspiration for targeted drug delivery.

The properties of nanomaterials make them promising and advantageous for use in drug delivery systems, but challenges arise from the immune system's recognition of exogenous nanoparticles, leading to their clearance and reduced targeting efficiency. Drawing inspiration from nature, this paper explores biomimetic strategies to transform recognizable nanomaterials into a "camouflaged state." The focal point of this paper is the exploration of bionic nanoparticles, with a focus on cell membrane-coated nanoparticles. These biomimetic structures, particularly those mimicking red blood cells (RBCs), white blood cells (WBCs), platelets, and cancer cells, demonstrate enhanced drug delivery efficiency and prolonged circulation. This article underscores the versatility of these biomimetic structures across diverse diseases and explores the use of hybrid cell membrane-coated nanoparticles as a contemporary trend. This review also investigated exosomes and protein bionic nanoparticles, emphasizing their potential for specific targeting, immune evasion, and improved therapeutic outcomes. We expect that this continued development based on biomimetic nanomaterials will contribute to the efficiency and safety of disease treatment.

CELL MEMBRANE COATED POLYMERIC NANOCARRIERS: A NOVEL DRUG DELIVERY APPROACH FOR THE TARGETED THERAPY OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis is a chronic inflammatory disorder that affects the joints and can lead to significant disability. RA may affect other parts of the body, leading to various issues including damage to the joints, deformity, disability, and reduced mobility. The pathogenesis of RA involves a complex interplay between genetic, environmental and immunological factors. The treatment of rheumatoid arthritis typically reduces inflammation, manages pain, stiffness and prevents joint damage. However, these medications have several side effects no single therapeutic remedy directly targets the disease. Researchers in the field are focused on developing new treatments that are more effective and have fewer side effects as well as understanding the underlying mechanisms of the disease. Some areas of current research include the use of nanotechnology such as cell membrane-coated nanoparticles for the treatment of RA as well as the development of new biologic drugs that target specific molecules involved in inflammation. The use of cell membrane-coated nanoparticles for the treatment of rheumatoid arthritis has several potential benefits including targeted drug delivery, reduced inflammation, improved safety and biocompatibility, and reduced frequency of administration. However, more research is needed to fully understand the potential benefits and limitations of this approach to develop effective cell membrane coated nanoparticle-based therapies for RA. In this review cell membrane-coated nanoparticles may become valuable for numerous biomedical problems.

Cancer cell membrane-coated nanoparticles: a promising anti-tumor bionic platform.

Nanoparticle (NP) drug delivery systems have shown promise in tumor therapy. However, limitations such as susceptibility to immune clearance and poor targeting in a complex intercellular environment still exist. Recently, cancer cell membrane-encapsulated nanoparticles (CCM-NPs) constructed using biomimetic nanotechnology have been developed to overcome these problems. Proteins on the membrane surface of cancer cells can provide a wide range of activities for CCM-NPs, including immune escape and homologous cell recognition properties. Meanwhile, the surface of the cancer cell membrane exhibits obvious antigen enrichment, so that CCM-NPs can transmit tumor-specific antigen, activate a downstream immune response, and produce an effective anti-tumor effect. In this review, we first provided an overview of the functions of cancer cell membranes and summarized the preparation techniques and characterization methods of CCM-NPs. Then, we focused on the application of CCM-NPs in tumor therapy. In addition, we summarized the functional modifications of cancer cell membranes and compiled the patent applications related to CCM-NPs in recent years. Finally, we proposed the future challenges and directions of this technology in order to provide guidance for researchers in this field.

Recent Advances of Multifunctional PLGA Nanocarriers in the Management of Triple-Negative Breast Cancer.

Even though chemotherapy stands as a standard option in the therapy of TNBC, problems associated with it such as anemia, bone marrow suppression, immune suppression, toxic effects on healthy cells, and multi-drug resistance (MDR) can compromise their effects. Nanoparticles gained paramount importance in overcoming the limitations of conventional chemotherapy. Among the various options, nanotechnology has appeared as a promising path in preclinical and clinical studies for early diagnosis of primary tumors and metastases and destroying tumor cells. PLGA has been extensively studied amongst various materials used for the preparation of nanocarriers for anticancer drug delivery and adjuvant therapy because of their capability of higher encapsulation, easy surface functionalization, increased stability, protection of drugs from degradation versatility, biocompatibility, and biodegradability. Furthermore, this review also provides an overview of PLGA-based nanoparticles including hybrid nanoparticles such as the inorganic PLGA nanoparticles, lipid-coated PLGA nanoparticles, cell membrane-coated PLGA nanoparticles, hydrogels, exosomes, and nanofibers. The effects of all these systems in various in vitro and in vivo models of TNBC were explained thus pointing PLGA-based NPs as a strategy for the management of TNBC.

Abstract A032: Cell membrane coated- Biomimetic biodegradable nanoparticles for tumor targeted delivery of THP-doxorubicin using polylactic acid based redox responsive polymer

Abstract Chemotherapy is a widely used systemic treatment modality for cancer treatment as it kills the rapidly dividing cells. However, the administered chemo-drugs cause systemic toxicity, have fast degradation rate at physiological conditions hence low bioavailability and poor tumor accumulation. These shortcomings can be mitigated by the use of tumor targeting drug delivery systems. The nanoparticles can further be tailor made according to physiological conditions of the tumor microenvironment. Herein, the redox responsive polymer has been synthesized by introducing the disulphide linkage in the polymer. The drug release profile indicated the release of the drug is more efficient in presence of 10mM Dithiothreitol(reducing agent for disulphide linkage) when compared to 0mM dithiothreitol. In this context, this study investigates the therapeutic efficacy of THP-doxorubicin encapsulated in polylactic acid based redox responsive nanoparticle(NP) whose surface have been modified with tumor (4T1) and macrophage (J774) cell membranes. The coated cell membrane provides advantages such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. The prepared nanoparticles have a hydrodynamic size of 210±10 nm with zeta potential of -30±3 mV. The cellular internalization studies of free drug vs the cell membrane coated NPs (CMNPs) were done and it was confirmed that CMNPs were internalized more efficiently in one hour drug incubation study. The same was confirmed when cancer cell proliferation inhibition assay was done, and half maximal inhibitory concentration of free drug, uncoated NPs and CMNPs were 0.31µM , 0.463µM and 0.137µM respectively. This study provides the synthesis and characterization of redox responsive polymer, preparation of cell membrane coated nanoparticles and in-vitro studies for the same. This study has a future scope in the field of personalized medicine at much cheaper price when compared to active targeting methods by antibodies, CART, proteins etc. Citation Format: Harshdeep Kaur, Harpal Singh, Neetu Singh. Cell membrane coated- Biomimetic biodegradable nanoparticles for tumor targeted delivery of THP-doxorubicin using polylactic acid based redox responsive polymer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A032.

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.