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。在本研究中，通过偶联甘草次酸（GA）、三苯膦（TPP）和阿霉素（DOX），将它们包裹在阳离子脂质体（CLs）中，然后包覆CLs表面，构建了分级给药系统HA-GDT-Lip。与医管局。HA-GDT-Lip纳米粒通过EPR效应在肿瘤组织中蓄积，进而实现CD44受体介导的肿瘤细胞特异性内吞作用，通过GA和TPP的联合作用，DOX可以顺利进入线粒体。理化性质分析表明，HA-GDT-Lip纳米颗粒大小均匀，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 可作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功效。