Tan Xiaoyan, Zhou Yanlin, Shen Li, Jia Han, Tan Xiaorong
Chongqing Anti-tumor Natural Drug Engineering Technology Research Center, Chongqing Three Gorges Medical College 404120 P. R. China
RSC Adv. 2019 Nov 13;9(63):37067-37078. doi: 10.1039/c9ra07096f. eCollection 2019 Nov 11.
For mitochondria-targeted nano-drug delivery systems against cancer, effectively targeting and releasing the drug into mitochondria are the keys to improve the therapeutic effect. In this study, mitochondria-targeted and reduction-sensitive micelles were developed to co-deliver doxorubicin (DOX) and evodiamine (EVO) for the treatment of metastatic breast cancer. After entering cancer cells, the micelles first targeted mitochondria through triphenylphosphonium cations. Then, the disulfide bonds of the micelles were cleaved by GSH, and both DOX and EVO were released near the mitochondria. The released EVO subsequently destroyed the mitochondrial membrane, resulting in a large amount of DOX entering the mitochondria and improving the anti-tumor effect of DOX. These mitochondria-targeted and reduction-sensitive micelles loaded with doxorubicin and evodiamine showed significant inhibition of the tumor cell growth both and .
对于针对癌症的线粒体靶向纳米药物递送系统而言，有效地将药物靶向并释放到线粒体中是提高治疗效果的关键。在本研究中，开发了线粒体靶向且对还原敏感的胶束，用于共递送阿霉素（DOX）和吴茱萸碱（EVO）以治疗转移性乳腺癌。进入癌细胞后，胶束首先通过三苯基膦阳离子靶向线粒体。然后，胶束的二硫键被谷胱甘肽（GSH）裂解，DOX和EVO均在线粒体附近释放。释放出的EVO随后破坏线粒体膜，导致大量DOX进入线粒体并提高DOX的抗肿瘤效果。这些负载阿霉素和吴茱萸碱的线粒体靶向且对还原敏感的胶束在体内和体外均显示出对肿瘤细胞生长的显著抑制作用。
