Probing the Superiority of Diselenium Bond on Docetaxel Dimeric Prodrug Nanoassemblies: Small Roles Taking Big Responsibilities

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2020-11, Vol.16 (45), p.e2005039-n/a
• Main Authors: Zuo, Shiyi, Sun, Bingjun, Yang, Yinxian, Zhou, Shuang, Zhang, Yu, Guo, Mengran, Sun, Mengchi, Luo, Cong, He, Zhonggui, Sun, Jin
• Format: Article
• Language: English
• Subjects: Anticancer properties; Blood circulation; Chemical compounds; Chemotherapy; dimeric prodrugs; Dimers; diselenide bond; Drug delivery systems; Drugs; Glutathione; Nanoparticles; Nanotechnology; redox‐responsive drug release; self‐assembly; Toxicity
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202005039

The current state of chemotherapy is far from satisfaction, restricted by the inefficient drug delivery and the off‐target toxicity. Prodrug nanoassemblies are emerging as efficient platforms for chemotherapy. Herein, three docetaxel dimeric prodrugs are designed using diselenide bond, disulfide bond, or dicarbide bond as linkages. Interestingly, diselenide bond‐bridged dimeric prodrug can self‐assemble into stable nanoparticles with impressive high drug loading (≈70%, w/w). Compared with disulfide bond and dicarbide bond, diselenide bond greatly facilitates the self‐assembly of dimeric prodrug, and then improves the colloidal stability, blood circulation time, and antitumor efficacy of prodrug nanoassemblies. Furthermore, the redox‐sensitive diselenide bond can specifically respond to the overexpressed reactive oxygen species and glutathione in tumor cells, leading to tumor‐specific drug release. Therefore, diselenide bond bridged prodrug nanoassemblies exhibit discriminating cytotoxicity between tumor cells and normal cells, significantly alleviating the systemic toxicity of docetaxel. The present work gains in‐depth insight into the impact of diselenide bond on the dimeric prodrug nanoassemblies, and provides promising strategies for the rational design of the high efficiency–low toxicity chemotherapeutical nanomedicines. To overcome the shortcomings of chemotherapy and exploit novel prodrug nanoassemblies, docetaxel (DTX) dimeric prodrugs are developed using diselenide bond, disulfide bond, or dicarbide bond as linkages. The diselenide bond‐bridged prodrug nanoassemblies, with impressive high drug loading (≈70%, w/w), superior self‐assembly ability, long blood circulation, and specific antitumor efficacy, provide great potential in the development of high‐efficient anticancer nanomedicines.