Cooperative bond scission by HRP/H_(2)O_(2)for targeted prodrug activation  

作　　者：Yunkang Tong Haiqiao Huang Haolan Li Mingle Li Wen Sun Jianjun Du Jiangli Fan Lei Wang Bin Liu Xiaoqiang Chen Xiaojun Peng 

机构地区：[1]State Key Laboratory of Fine Chemicals,Frontiers Science Center for Smart Materials,Dalian University of Technology,Dalian 116024,China [2]State Key Laboratory of Fine Chemicals,College of Materials Science and Engineering,Shenzhen University,Shenzhen 518060,China

出　　处：《Chinese Chemical Letters》2024年第12期399-404,共6页中国化学快报（英文版）

基　　金：the National Natural Science Foundation of China(No.22090011);the Fundamental Research Funds for China Central Universities(No.DUT22LAB608)for financial support。

摘　　要：The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoid ing their side effects.The main challenge lies in the fast and effective release of the parent drugs at the desired site under specific stimuli.Herein,a cooperative prodrug activation approach with exogenous na tive enzyme and endogenous tumor small molecule biomarkers was developed.Chemically,precursor of methylene blue(MB)and resorufin(RSF)react with horseradish peroxidase(HRP)/hydrogen perox ide(H_(2)O_(2))to quickly and quantitatively release parent dyes and drugs containing amines or carboxylic acids.The application of this approach in mammalian cells was demonstrated with cooperative-activated photodynamic therapy based on a precursor of MB.Compared with free MB,much higher selectivity to ward cancer cells was achieved with this approach as evaluated by the selectivity index(SI).This study provides a new method for fast and effective targeted prodrug activation with no need for antibody mod ification compared with traditional enzyme/prodrug therapy.

关 键 词：PRODRUG ENZYME Tumor microenvironment Hydrogen peroxide Photodynamic therapy Fluorescent probe 

分 类 号：R914[医药卫生—药物化学]