叶酸介导的雷公藤甲素外泌体靶向给药系统抗恶性黑色素瘤体内外评价

In this study, exosomes derived from human malignant melanoma A375 cells were used as carriers, the folate receptor highly expressed on the surface of tumor cells was targeted, and triptolide, a traditional Chinese medicine, was used as a model drug to prepare the exosome-targeted drug delivery system FA - Exo/TPL, and its in vitro characteristics and in vivo anti-tumor effects were characterized and evaluated. Exosomes were collected by gradient centrifugation, and the drug was loaded after folate-targeted modification. The prepared FA - Exo/TPL had a particle size of about 100 nm and a saucer-shaped double-layer membrane structure, with a relatively high drug encapsulation efficiency and drug loading capacity. In vitro studies showed that FA - Exo/TPL could be abundantly taken up by melanoma cells, thereby enhancing the drug's effects of inhibiting cell proliferation and promoting cell apoptosis. The results of in vivo experiments indicated that FA - Exo/TPL could effectively inhibit the growth of tumor tissues, prolong the survival period of tumor-bearing nude mice, and significantly reduce the systemic toxicity of the drug, achieving the effects of enhancing efficacy and reducing toxicity. Animal welfare and experimental procedures all followed the regulations of the Animal Ethics Committee of Fudan University Shanghai Cancer Center. This study provides new ideas and methods for the pharmaceutical research of triptolide against malignant melanoma.

本研究以人恶性黑色素瘤A375细胞来源的外泌体为载体, 以肿瘤细胞表面高表达的叶酸受体为靶点, 以.中药雷公藤甲素为模型药物, 制备外泌体靶向给药系统FA-Exo/TPL, 并对其体外特性和体内抑瘤效果进行表征和.评价。采用梯度离心法收集外泌体, 叶酸靶向修饰后包载药物, 制备成的 FA-Exo/TPL粒径在 100 nm左右, 呈茶托.状双层膜结构, 对药物具有较高的包封率和载药量。体外研究显示, FA-Exo/TPL可被黑色素瘤细胞大量摄取, 从而.增强了药物抑制细胞增殖和促进细胞凋亡的作用。体内实验结果表明, FA-Exo/TPL能有效抑制肿瘤组织的生长,.延长荷瘤裸鼠的生存期, 且能显著降低药物的系统毒性, 起到增效减毒的作用。动物福利和实验过程均遵循复旦大.学附属肿瘤医院动物伦理委员会的规定。本研究为雷公藤甲素抗恶性黑色素瘤的制剂学研究提供了新的思路和.方法。