Novel Nanococktail of a Dual PI3K/mTOR Inhibitor and Cabazitaxel for Castration-Resistant Prostate Cancer

文献类型： 外文期刊

第一作者： Huang, Yee

作者： Huang, Yee;Xue, Xiangdong;Li, Xiaocen;Jia, Bei;Li, Yuanpei;Pan, Chong-Xian;Lin, Tzu-Yin;Pan, Chong-Xian

作者机构：

关键词： disulfide cross-linked micelles; gedatolisib; PI3K pathways; synergistic antitumor effects

期刊名称：ADVANCED THERAPEUTICS （ 影响因子：5.003； 五年影响因子：5.445 ）

ISSN：

年卷期： 2020 年 3 卷 10 期

页码：

收录情况： SCI

摘要： Prognosis for castration-resistant prostate cancer (CRPC) is poor, and no effective therapeutic regimen is yet known. The PI3K/Akt/mTOR pathway plays a predominant role and may be a promising molecular target for CRPC. However, the toxicity of the dual PI3K inhibitors in clinical trials limits their clinical efficacy for CRPC. To solve this problem, a highly integrated precision nanomedicine strategy is employed to molecularly and physically target CRPC through enhanced targeted drug delivery efficiency and reduced unwanted side-effects. Gedatolisib (Ge), a potent inhibitor of PI3K/mTOR, is formulated into disulfide cross-linked micelle platform (NanoGe), which exhibits excellent water solubility, small size, excellent stability with redox stimulus-responsive disintegration, and preferential uptake at tumor sites. NanoGe improves the anti-neoplastic effect of free Ge by 53 times in PC-3M cells and 13 times in C4-2B cells, through its enhanced uptake via caveolae- and clathrin-mediated endocytic pathways and the subsequent inhibition of the PI3K/mTOR pathway, resulting in Bax/BcI-2-dependent apoptosis. In vivo, NanoGe shows superior efficacy than free Ge, and synergizes with nanoformulated cabazitaxel (NanoCa) as a nanococktail format to achieve a cure rate of 83%. Taken together, the results of this study demonstrate the potency of NanoGe in combination with NanoCa against CRPC.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序