A ROS-responsive,self-immolative and self-reporting hydrogen sulfide donor with multiple biological activities for the treatment of myocardial infarction  

作　　者：Mengyun Yao Yifei Lu Lin Shi Yong Huang Qing Zhang Jianglin Tan Ping Hu Jianxiang Zhang Gaoxing Luo Ning Zhang 

机构地区：[1]Institute of Burn Research,Southwest Hospital,State Key Lab of Trauma,Burn and Combined Injury,Chongqing Key Laboratory for Disease Proteomics,Third Military Medical University(Army Medical University),Chongqing 400038,China [2]College of Pharmacy,Jinan University,Guangzhou 511443,China [3]Department of Pharmaceutics,College of Pharmacy,Third Military Medical University(Army Medical University),Chongqing 400038,China

出　　处：《Bioactive Materials》2022年第3期168-182,共15页生物活性材料（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.82002044&82002045);China Postdoctoral Science Foundation(No.2019M663976);and Natural Science Foundation of Chongqing(No.cstc2020jcyj-bshX0014).

摘　　要：Myocardial infarction(MI),as one of the leading causes of global death,urgently needs effective therapies.Recently,hydrogen sulfide(H2S)has been regarded as a promising therapeutic agent for MI,while its spatiotemporally controlled delivery remains a major issue limiting clinical translation.To address this limitation,we designed and synthesized a novel H2S donor(HSD-R)that can produce H2S and emit fluorescence in response to reactive oxygen species(ROS)highly expressed at diseased sites.HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo.Therapeutically,HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model.Mechanistically,myocardial protection is achieved by reducing cardiomyocyte apoptosis,attenuating local inflammation,and promoting angiogenesis.Furthermore,inhibition of typical pro-apoptotic genes(Bid,Apaf-1,and p53)played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection,which were identified as new therapeutic targets of H2S against myocardial ischemia injury.This ROS-responsive,self-immolative,and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

关 键 词：Hydrogen sulfide donor Reactive oxygen species Myocardial infarction Molecular imaging Theranostic agent 

分 类 号：R54[医药卫生—心血管疾病]