Activatable and Self-Monitoring Hydrogen Sulfide-Based Molecular Senomorphics for Visualized Regulation of Cellular Senescence  

作　　者：Jili Li Yuqi Xie Jian Wang Linlin Wang Yinghao Xia Yanlan Liu Weihong Tan 

机构地区：[1]Molecular Science and Biomedicine Laboratory(MBL),State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Aptamer Engineering Center of Hunan Province,Hunan University,Changsha,Hunan 410082 [2]The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou,Zhejiang 310022 [3]Institute of Molecular Medicine(IMM),Renji Hospital,Shanghai Jiao Tong University School of Medicine,College of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240

出　　处：《CCS Chemistry》2023年第12期2897-2909,共13页中国化学会会刊（英文）

基　　金：supported by the National Natural Science Foundation of China(grant nos.NSFC22274044 and 21877031);the National Key Research and Development Program of China(grant no.2020YFA0210802);the Science and Technology Innovation Program of Hunan Province(grant no.2018RS3043).

摘　　要：Specific regulation of the senescence-associated secretory phenotype(SASP)is vital to block senescence-induced detrimental cellular plasticity.Recently,some chemical compounds called senomorphics have demonstrated such potential,but it remains challenging to achieve site-specific activation and real-time monitoring of the action of senomorphics,posing great obstacles for transformable applications.Here,we report a tailor-made hydrogen sulfide(H_(2)S)donor(Lyso-FH_(2)S-Gal)as a new class of molecule senomorphics for spatially controlled delivery of H_(2)S for visualization of regulation of cellular senescence.It comprises four functional moieties in a single molecular structure,including a lysosome-targeting group for cell recognition,a lysosomal enzyme-cleaved scaffold for site-specific activation,thiocarbamate as the H_(2)S precursor,and a switchable fluorophore for concurrent selfreporting of H_(2)S release and senescence imaging.Lyso-FH_(2)S-Gal exhibited remarkable response selectivity,sustained H_(2)S release,and 141-fold fluorescence enhancement.In cellular models,Lyso-FH_(2) S-Gal preferentially enriched in senescent cells over nonsenescent cells,and alleviated the levels of SASP and reactive oxygen species(ROS)in senescent cells,while remaining inert in nonsenescent cells.More impressively,it efficiently inhibited the SASPmediated crosstalk between senescent cells and surrounding nonsenescent cells,thereby preventing senescence propagation.This work offers a useful molecular tool with the hope for controlled intervention of senescence-related important biological processes.

关 键 词：cellular senescence hydrogen sulfide donor molecular senomorphics visualized release cellular communications 

分 类 号：R73[医药卫生—肿瘤]