文献类型：期刊文献

英文题名：Biomimic Binding Affinity Gradients Triggered GSH-Response of Core-Shell Nanoparticles for Cascade Chemo/Chemodynamic Therapy

作者：Wang, Qinghua[1];Li, Xianglong[1];Mao, Jiayi[1];Qin, Xing[1];Yang, Shaobo[1];Hao, Jina[1];Guan, Mengjia[1];Cao, Yuanyuan[1];Li, Yongsheng[1,2]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & 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;[2]Shihezi Univ, Sch Chem & Chem Engn, Key Lab Green Proc Chem Engn Xinjiang Bingtuan, Shihezi 832003, Peoples R China

年份：2022

卷号：11

期号：2

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20214511127958);WOS:【SCI-EXPANDED(收录号:WOS:000715139500001)】；

基金：The authors acknowledge the financial supports from the National Natural Science Foundation of China (Nos. 51621002, 51972112, and 22005096), Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX03), Basic Research Program of Shanghai Municipal Government (Grant Nos. 21JC1406003 and 19JC1411700), and the Leading Talents in Shanghai in 2018 and the 111 project (B14018), Shanghai Sailing program (20YF1410100). All animal experiments were performed in compliance with the Guidelines for the Care and Use of Research Animals established by the East China University of Science and Technology Animal Studies (ECUST-2020-04001).

语种：英文

外文关键词：biomimic; chemodynamic therapy; glutathione response; intracellular copper trafficking; polydopamine

摘要：In eukaryotes and prokaryotes, some copper transportations driven by gradient copper-binding affinities exhibit typical glutathione (GSH)-responsive features. Inspired by these delicate endogenous processes, a biomimic copper-ion mediated GSH-responsive nanomedicine is designed based on the gradient copper-binding strengths between polydopamine (PDA) species and GSH. The nanomedicine is constructed as core-shell nanoparticles with copper-polydopamine (Cu-PDA) coordinated shell and micellar core encapsulating chemotherapeutic drug of beta-lapachone (beta-lapa). In tumor cells, the excess intracellular GSH will reduce and extract the Cu(II) from the Cu-PDA network, triggered by the binding affinity gradients between Cu-PDA and Cu-GSH, resulting in the breaking of the shell and the releasing of beta-lapa and Fenton agent copper. The additional Fenton reaction of copper ions induces excess oxidative damage of tumor cells assisted by the abundant H2O2 amplified by beta-lapa, achieving cascade anticancer effects combining chemodynamic therapy with chemotherapy. This multilevel anticancer system exhibits an efficient tumor inhibitory rate and a negligible systematic toxicity for normal organs in vivo, presenting a new bioinspired GSH-responsive strategie to develop stimuli-responsive structures.