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.