文献类型：期刊文献

英文题名：GSH-Responsive Organosilica Hybrid Nanosystem as a Cascade Promoter for Enhanced Starvation and Chemodynamic Therapy

作者：Wu, Huan[1];Li, Xianglong[1];Liu, Shi[1];Wang, Qinghua[1];Cao, Yuanyuan[1];Hao, Ji-Na[1];Li, Yongsheng[1]

机构：[1]East China Univ Sci & Technol, Frontier Sci Ctr Mat Biol & Dynam Chem, Shanghai Engn Res Ctr Hierarch Nanomat,Minist Edu, Sch Mat Sci & Engn,Lab Low Dimens Mat Chem,Key La, Shanghai 200237, Peoples R China

年份：2023

卷号：12

期号：2

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20224513088613);WOS:【SCI-EXPANDED(收录号:WOS:000876109900001)】；

基金：H.W. and X.L. contributed equally to this work. This work was financially supported by the National Natural Science Foundation of China (Nos. 51621002, 51972112, 52172279, 21805087), Shanghai Municipal Science and Technology Major Project (grant: 2018SHZDZX03), Basic Research Program of Shanghai (21JC1406003 and 19JC1411700), Leading Talents in Shanghai in 2018, Shanghai Rising Star Program (21QA1402200), the Natural Science Foundation of Shanghai (21ZR1416600), the 111 project (B14018). Animal experiments were carried out according to the protocol approved by the Laboratory Animal Management Committee of East China University of Science and Technology (approval number: ECUST-2020-04001).

语种：英文

外文关键词：cascade reaction; chemodynamic therapy; GSH-responsive degradability; hybrid nanoparticles; starvation therapy

摘要：Glucose oxidase (GOD)-mediated starvation therapy (ST) that causes intratumoral glucose depletion is a promising strategy for tumor treatment. However, the ultimate efficacy is inevitably limited by tumor hypoxia, as oxygen is a key component in the consumption of glucose by GOD. In this study, a kind of glutathione (GSH)-responsive organosilica hybrid micelles loaded with Mn3O4 and GOD (denoted as Mn3O4@PDOMs-GOD) is ingeniously designed for enhanced ST and chemodynamic therapy (CDT). Specifically, the internalized Mn3O4@PDOMs-GOD in tumor cells consumes intracellular glucose and oxygen (O-2) under the catalysis of GOD to generate hydrogen peroxide (H2O2), which is subsequently decomposed by Mn3O4 to liberate O-2. This cyclically regenerated O-2 will form a virtuous cycle of O-2 and H2O2 compensation to enhance the ST outcome. Meanwhile, Mn3O4 can oxidize and deplete the overexpressed GSH in the tumor microenvironment (TME) to release Mn2+, which then catalyzes H2O2 into highly toxic hydroxyl radicals (center dot OH) to accomplish chemodynamic therapy (CDT). Both in vitro and in vivo experiment results demonstrate the significant antitumor efficacy of Mn3O4@PDOMs-GOD by the cooperatively enhanced ST and CDT, suggesting the feasibility to develop promising therapeutic platforms with higher treatment efficacies.