Cabazitaxel prodrug nanoassemblies with branched chain modifications: Narrowing the gap between efficacy and safety

• DOI: 10.1016/j.jconrel.2023.07.012
• Publication Date: 2023-07-22T11:40:15Z
• Authors: Hezhen Xu; Shiyi Zuo; Danping Wang; Yu Zhang; Wenxiao Li; Lingxiao Li; Tian Liu; Yuanhao Yu; Qingzhi Lv; Zhonggui He; Jin Sun; Bingjun Sun
• Keywords: Cabazitaxel; Biosafety

The clinical application of cabazitaxel (CTX) is restricted by severe dose-related toxicity, failing to considering therapeutic efficacy and safety together. Self-assembled prodrugs promote new drug delivery paradigms as they can self-deliver and self-formulate. However, the current studies mainly focused on the use of straight chains to construct self-assembled prodrugs, and the role of branched chains in prodrug nanoassemblies remains to be clarified. In this study, we systematically explored the structure-function relationship of prodrug nanoassemblies using four CTX prodrugs that contained branched chain aliphatic alcohols (BAs) with different alkyl lengths. Overall, CTX-SS-BA20 NPs with the proper alkyl length exhibited significant improvements in both antitumor efficacy and biosafety. Furthermore, compared with straight chain (SC) modified prodrug nanoassemblies (CTX-SS-SC20 NPs), CTX-SS-BA20 NPs still hold great therapeutic promise due to its good biosafety. These findings illustrated the significance of BAs as modified chains in designing prodrug nanoassemblies for narrowing the efficacy-to-safety gap of cancer therapy.