The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

作者：Shuo Wang, Tian Liu, Yuetong Huang, Chaoying Du, Danping Wang, Xiyan Wang, Qingzhi Lv, Zhonggui He, Yinglei Zhai, Bingjun Sun, Jin Sun · 发表于：Acta Pharmaceutica Sinica B · 年份：2023 · DOI：10.1016/j.apsb.2023.09.017 · 被引用次数：33 · 研究领域：Cancer Treatment and Pharmacology、Nanoparticle-Based Drug Delivery、Colorectal Cancer Treatments and Studies

The self-assembly prodrugs are usually consisted of drug modules, activation modules, and assembly modules. Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies. This study designed four docetaxel (DTX) prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules (C16, C18, C20, and C24). The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’ sensitivity. The extension of the carbon chains improved the prodrugs’ self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity. The use of C20 can balance efficacy and safety. These results provide a great reference for the rational design of prodrug nanoassemblies.