Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, PR China.
Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, PR China.
Eur J Med Chem. 2022 Nov 5;241:114648. doi: 10.1016/j.ejmech.2022.114648. Epub 2022 Aug 5.
Chemotherapy targeting mitochondrial is a faster and more sensitive anti-tumor therapy strategy. In this study, a hierarchical drug delivery system HA-GDT-Lip was constructed by coupling glycyrrhetinic acid (GA), triphenylphosphine (TPP), and doxorubicin (DOX), encapsulating them in cationic liposomes (CLs), then coating the surface of CLs with HA. HA-GDT-Lip nanoparticles can be accumulated in tumor tissue through the EPR effect, then achieve tumor cell-specific endocytosis mediated by the CD44 receptor, DOX can be successfully delivered into mitochondria through the combined action of GA and TPP. Physicochemical properties analysis showed that HA-GDT-Lip nanoparticles were uniform in size and spherical in shape. In vitro cell experiments showed that HA-GDT-Lip had high cell uptake efficiency and mitochondrial targeting ability. In addition, HA-GDT-Lip could induce MPTP opening and accelerate cell apoptosis. Meanwhile, HA-GDT-Lip showed excellent antitumor activity and in vivo safety in tumor-bearing nude mice. In conclusion, HA-GDT-Lip may serve as a promising mitochondrial delivery system to reduce the side effects of anticancer drugs and improve their antitumor efficacy.
靶向线粒体的化疗是一种更快、更敏感的抗肿瘤治疗策略。在这项研究中，通过偶联甘草次酸（GA）、三苯基膦（TPP）和阿霉素（DOX），构建了一种分级药物传递系统 HA-GDT-Lip，将它们包裹在阳离子脂质体（CLs）中，然后在 CLs 表面涂覆 HA。HA-GDT-Lip 纳米颗粒可以通过 EPR 效应在肿瘤组织中积累，然后通过 CD44 受体介导的肿瘤细胞特异性内吞作用，GA 和 TPP 的联合作用可以将 DOX 成功递送到线粒体中。物理化学性质分析表明，HA-GDT-Lip 纳米颗粒粒径均一，呈球形。体外细胞实验表明，HA-GDT-Lip 具有较高的细胞摄取效率和线粒体靶向能力。此外，HA-GDT-Lip 可以诱导 MPTP 开放并加速细胞凋亡。同时，HA-GDT-Lip 在荷瘤裸鼠中表现出优异的抗肿瘤活性和体内安全性。总之，HA-GDT-Lip 可能成为一种有前途的线粒体递送系统，以减少抗癌药物的副作用并提高其抗肿瘤疗效。
