Shen Jie, Wang Qiwen, Fang Jie, Shen Wangxing, Wu Dan, Tang Guping, Yang Jie
School of Medicine, Zhejiang University City College Hangzhou 310015 P. R. China
Heart and Vascular Center, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310003 Zhejiang P. R. China.
RSC Adv. 2019 Nov 15;9(64):37232-37240. doi: 10.1039/c9ra07051f. eCollection 2019 Nov 13.
To obtain an efficient dual-drug release and enhance therapeutic efficiency for combination chemotherapy, a glutathione (GSH)-responsive therapeutic amphiphilic polyprodrug copolymer (mPEG--PCPT) is synthesized to load doxorubicin (DOX) hydrophobic and π-π stacking interaction. In this nanomedicine system (mPEG--PCPT/DOX), the ratio of the two drugs can be easily modulated by changing the loading content of DOX. The drug release curves and laser confocal images suggested that the release of CPT and DOX is induced through a "release promotes release strategy": after internalization into tumor cells, the disulfide bonds in the nanomedicine are cleaved by glutathione (GSH) in the cytoplasm and then lead to the release of CPT. Meanwhile, the disassembly of nanomedicine immediately promotes the co-release of DOX. The optimum dose ratio of CPT and DOX is evaluated the combination index (CI) value using HepG-2 cells. The results of cell apoptosis and cell viability prove the better synergistic efficiency of the nanomedicine than free drugs at the optimum dose ratio of 1. Consequently, this stimuli-responsive synergistic chemotherapy system provides a direction for the fabrication of nanomedicines possessing promising potential in clinical trials.
为实现高效的双药释放并提高联合化疗的治疗效果，合成了一种谷胱甘肽（GSH）响应性治疗性两亲性聚前药共聚物（mPEG-PCPT），通过疏水作用和π-π堆积相互作用负载阿霉素（DOX）。在这种纳米药物体系（mPEG-PCPT/DOX）中，两种药物的比例可通过改变DOX的负载量轻松调节。药物释放曲线和激光共聚焦图像表明，CPT和DOX的释放是通过“释放促进释放策略”诱导的：纳米药物内化进入肿瘤细胞后，纳米药物中的二硫键被细胞质中的谷胱甘肽（GSH）裂解，进而导致CPT释放。同时，纳米药物的解体立即促进DOX的共同释放。使用HepG-2细胞通过联合指数（CI）值评估CPT和DOX的最佳剂量比。细胞凋亡和细胞活力结果证明，在最佳剂量比为1时，纳米药物的协同效率优于游离药物。因此，这种刺激响应性协同化疗系统为制备在临床试验中具有广阔前景的纳米药物提供了方向。
