Branched module-modified SN38 prodrug nanoassemblies for improved colorectal cancer therapy:Effectively balance efficacy and safety  

作　　者：Qing Wang Shiyi Zuo Shufang Zheng Cuiyun Liu Yaqiao Li Jiayu Guo Danping Wang Shuo Wang Wenjing Wang Bowen Zhang Minglong Huang Xianbao Shi Jin Sun Zhonggui He Bingjun Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Joint International Research Laboratory of Intelligent Drug Delivery Systems,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China [3]School of Chemical Engineering,The University of Adelaide,Adelaide,SA 5005,Australia [4]Department of Pharmacy,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China

出　　处：《Nano Research》2025年第1期572-585,共14页纳米研究（英文版）

基　　金：gotapproval from the Institutional Animal Ethical Care Committee(IAEC)of Shenyang Pharmaceutical University(ethical code:SYPU-IACUC-2022-0302-010).

摘　　要：The clinical utility of irinotecan is restricted by individual variability in carboxylesterase expression.Direct administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alternative due to its potent anti-tumor efficacy.However,the undesirable properties of SN38,such as poor water solubility and nontarget toxicity,present significant hurdles to its clinical development.Prodrug nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective activation.In modular design,the modification module plays a crucial role in improving the self-assembly capability of prodrugs.While current studies mainly focus on using straight aliphatic chains for prodrug design,branched aliphatic chains emerge as superior alternatives warranting further investigation.In this study,we selected 2-heptylundecanol(BAlc18)as modification module to construct an SN38 prodrug.Through exquisite design,SN38-SS-BAlc18 NPs integrated prominent properties in selfassembly capability,specific activation and biocompatibility,resolving the challenges of irinotecan and SN38,ultimately demonstrating excellent anti-tumor efficacy.This exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.

关 键 词：IRINOTECAN SN38 prodrug nanoassemblies disulfide bonds branched aliphatic chains 

分 类 号：R735.37[医药卫生—肿瘤]