期刊
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 16, 期 3, 页码 337-349出版社
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2021.02.002
关键词
Diselenide bond; Homodimeric prodrug; Docetaxel; Self-assembly; Redox responsive
资金
- China Postdoctoral Innovative Talents Support Program [BX20190219]
- China Postdoctoral Science Foundation [2019M661134]
- National Natural Science Foundation of China [81872816]
The linkages in homodimeric prodrugs play a crucial role in self-assembly, in vivo fate, and antitumor activity. Prolonged linkages can facilitate self-delivery of drugs, improve stability and targeting of nanoassemblies, while reducing cytotoxicity in tumor cells.
Homodimeric prodrug-based self-assembled nanoparticles, with carrier-free structure and ultrahigh drug loading, is drawing more and more attentions. Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage. The influence of the linkages on the self-assembly, in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research. Herein, three docetaxel (DTX) homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages. Interestingly, compared with the other two linkages, the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs, thus improving the stability, circulation time and tumor targeting of prodrug nanoassemblies. Besides, the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells. Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells, their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells, which finally turned the table. Our study illustrates the crucial role of linkages in homodimeric prodrugs, and gives valuable proposal for the development of advanced nano-DDS for cancer treatment. (C) 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V.
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