From prodrug to pro-prodrug:hypoxia-sensitive antibody–drug conjugates

作     者：Yanming Wang Dian Xiao Jiaguo Li Shiyong Fan Fei Xie Wu Zhong Xinbo Zhou Song Li 

作者机构：National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and Toxicology100850 BeijingChina Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of Sciences310022 HangzhouZhejiangChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2022年第7卷第2期

页      面：369-371页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was funded by the Chinese National Natural Science Foundation[grant number 81872736 and 81903451] the China Postdoctoral Science Foundation[grant number 2019M664015] 

主　　题：drug clinical 

摘      要：Dear Editor,Antibody‒drug conjugates(ADCs),famous as biological targeting prodrugs,are gradually revolutionizing clinical cancer ***,less than 1%of the dosed ADCs accumulate in the tumors.1 Therefore,the nonspecific release of the highly toxic payload(MMAE et al.,10−12–10−10 M)is a real threat,which could induce severe off-target toxicity.2 This danger necessitates strict requirements for the design of the *** date,the mainstream enzyme cleavable linkers,includingβ-glucuronidase cleavable linkers,sulfatase-cleavable linkers,and the most popular cathepsin cleavable linkers(valine-citrulline linker),all face this nonspecific release problem,3 because their cleaving enzymes are widely distributed with no significant difference in their quantities between tumor tissues and normal tissues.