Ai Xiaoyu, Sun Jin, Zhong Lu, Wu Chunnuan, Niu Handong, Xu Tao, Lian He, Han Xiaopeng, Ren Guolian, Ding Wenya, Wang Jia, Pu Xiaohui, He Zhonggui
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, 110016, P. R. China.
Macromol Biosci. 2014 Oct;14(10):1415-28. doi: 10.1002/mabi.201400149. Epub 2014 Jun 20.
A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P(5k)SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P(5k)LV (P(5k)LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P(5k)SSLV-DOX, P(5k)LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P(5k)SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P(5k)LV-DOX nanomicelles. In conclusion, the redox-responsive P(5k)SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.
开发了一种氧化还原响应性聚乙二醇（PEG）可脱落共聚物，即二硫键连接的聚乙二醇5000 - 赖氨酸 - 二琥珀酸生育酚（P(5k)SSLV），它在水性条件下可自组装成纳米胶束，并能触发肿瘤细胞内封装药物的快速释放。进一步制备了对还原不敏感的负载阿霉素（DOX）的P(5k)LV（P(5k)LV - DOX）纳米胶束。然后，针对体外释放、细胞毒性、细胞摄取和凋亡，对P(5k)SSLV - DOX、P(5k)LV - DOX和DOX - Sol进行了直接比较。结果表明，与P(5k)LV - DOX纳米胶束相比，P(5k)SSLV - DOX纳米胶束具有更快的DOX释放速度、更高的抗肿瘤活性以及更多的DOX聚集在细胞核中。总之，氧化还原响应性P(5k)SSLV纳米胶束在通过肿瘤触发细胞内快速释放来改善化疗方面可能具有巨大潜力。本研究结果还揭示了此类直接比较研究在纳米医学转化研究中的重要性。
