Tailoring modification modules of paclitaxel prodrug nanoassemblies to manipulate efficacy and tolerance

紫杉醇 前药 药理学 纳米技术 材料科学 医学 化疗 内科学
作者
Yixin Sun,Simeng Wang,Jinrui Liu,Danping Wang,Xiaoxiao Zhang,Yaqiao Li,Lingxiao Li,Dun Zhou,Jin Sun,Zhonggui He,Tianhong Zhang,Qikun Jiang,Bingjun Sun
出处
期刊:Nano Today [Elsevier]
卷期号:56: 102275-102275
标识
DOI:10.1016/j.nantod.2024.102275
摘要

Carrier-free prodrug nanoassemblies have emerged as promising strategies to improve the therapeutic index of chemotherapeutics. Generally, prodrugs are composed of drug modules, response modules and modification modules. However, how to optimize the pharmacodynamics and tolerance of prodrug nanoassemblies by designing the structure of modification modules remains to be explored. Herein, four redox-cleavable prodrugs were synthesized by chemically coupling different branched-chain fatty alcohols with paclitaxel (PTX-SS-C16 NPs, PTX-SS-C18 NPs, PTX-SS-C20 NPs, PTX-SS-C24 NPs). Notably, the assembly ability of the prodrug nanoassemblies increased with the extension of the carbon chain of the modification modules. The redox-responsive rates of the prodrug nanoassemblies decreased with the extension of the carbon chain length. Among them, PTX-SS-C16 NPs and PTX-SS-C18 NPs displayed high redox responsiveness and antitumor efficacy. PTX-SS-C18 NPs and PTX-SS-C20 NPs possessed superior safety. However, PTX-SS-C24 NPs exhibited undesirable tumor selectivity and tolerance due to the excessive carbon chain length and inferior redox-responsive rate. This work demonstrated that tailoring the modification modules could simultaneously optimize the antitumor efficacy and tolerance of prodrug nanoassemblies for highly efficient therapeutics.
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