Modularly engineered prodrug-nanoassemblies for cancer therapy:Nonpharmacological moiety dominating delivery fates  

作　　者：Yuequan Wang Qian Qiu Rui Liao Xinhui Wang Ziran Zhou Xuanbo Zhang Haotian Zhang Zhonggui He Shenwu Zhang Cong Luo Jin Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Life Science and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Nano Research》2023年第1期980-990,共11页纳米研究（英文版）

基　　金：This work was financially supported by Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452);the Liaoning Revitalization Talents Program(No.XLYC1907129);the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06);the China Postdoctoral Science Foundation(Nos.2020M670794 and 2021MD703858).

摘　　要：Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.

关 键 词：small-molecule prodrug PACLITAXEL self-assembly ability nonpharmacological moiety modular engineering delivery fate 

分 类 号：O62[理学—有机化学]