Cross-linked lipoic acid nanocapsules serve as H_(2)O_(2) amplifier to strengthen the H_(2)O_(2)-sensitive prodrug activation  

作　　者：Jiangbing Tan Pei Jing Xiao Xiao Yulong Liao Chunyan Liao Shiyong Zhang 

机构地区：[1]College of Biomedical Engineering and National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China [2]Department of Pharmacy,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China

出　　处：《Science China Chemistry》2023年第9期2654-2663,共10页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (22201193 and 21975165);the Innovative Research Team Program of Sichuan Province (2021JDTD0015);the National Natural Science Foundation of Sichuan Province (2023NSFSC1691)。

摘　　要：The H_(2)O_(2) -triggered prodrug activation represents a hot topic while the low H_(2)O_(2) level of cancer cells hindered the complete activation of parent drugs and resulted in the poor therapeutic effect. Here, we developed an H_(2)O_(2) amplifier fabricated by crosslinked lipoic acid nanocapsules(cLANCs), which would selectively elevate the intracellular H_(2)O_(2) level of cancer cells 3.4-fold higher than that of untreated cancer cells so as to speed up the activation of parent drug from the loaded prodrugs(Pro-5-FU). The cytotoxicity showed that the killing effect of Pro-5-FU loaded in cLANCs(Pro-5-FU@cLANCs) arrived up to 1.6-time higher than that of Pro-5-FU alone against A549 cells, and was even close to free 5-FU. The in vivo anticancer evaluation gave the tumor inhibition rate(TIR) and survival rate(SR) of Pro-5-FU@cLANCs against A549 tumor-bearing nude mice up to 73.1% and 80%,respectively, much higher than those of Pro-5-FU(TIR: 41.2%, SR: 20%) or free 5-FU(TIR: 50.6%, SR: 0%). This nanodrug constructed the first example that utilizes the drug carriers as H_(2)O_(2) amplifier to strengthen the prodrug activation.

关 键 词：cancer therapy prodrug activation H_(2)O_(2)amplifier drug carrier 

分 类 号：TQ460.1[化学工程—制药化工]