细胞膜纳米载体通常是通过用细胞膜提取物修饰纳米颗粒表面来构建的，这有一个直接的好处，即赋予纳米载体基于其原始细胞类型的靶向能力。然而，由于细胞膜部分带有强负电荷，通过基于细胞膜的纳米粒子递送核酸货物是困难的。在这项研究中，我们开发了一种基于癌细胞膜的药物递送系统 cMDS，用于高效 siRNA 递送。同时，基因载体本身刺激的癌症特异性免疫反应可以提供协同抗癌能力。通过超声制备cMDS，并用CT26细胞培养物检测其转染效率和抗癌能力。通过MTT和红细胞溶血试验来评估cMDS的安全性，同时在皮下肿瘤模型中研究其靶向基因递送和强免疫刺激。此外，通过蛋白质芯片分析揭示了cMDS详细的抗癌免疫刺激机制。cMDS为球形核壳结构。其在体外表现出较高的转染效率和抗癌能力。在动物实验中，静脉注射cMDS/siStat3复合物可有效抑制结肠癌的生长。此外，蛋白芯片分析结果提示cMDS影响免疫细胞的迁移和趋化性。cMDS表现出明显的肿瘤组织特异性聚集特性和较强的免疫刺激能力。它是一种先进的靶向基因传递系统，具有强大的免疫治疗特性。© 2023 Li et al.

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.© 2023 Li et al.