文献类型：期刊文献

英文题名：A senolysis-based theragnostic prodrug strategy towards chronic renal failure

作者：Song, Yihe[1];Li, Xinming[1];Shi, Donglei[1,2];Sun, Tianyue[1];Liu, Wenwen[3];Li, Xiaokang[1];Qiao, Sicong[1];Chen, Xin[1];Guo, Yuan[2];Li, Jian[1,3,4,5]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, Frontiers Sci Ctr Materiobiol & Dynam Chem,Sch Ph, Shanghai Key Lab New Drug Design,State Key Lab Bi, Shanghai 200237, Peoples R China;[2]Northwest Univ, Coll Chem & Mat Sci, Key Lab Synthet & Nat Funct Mol, Minist Educ, Xian 710127, Peoples R China;[3]Hainan Univ, Coll Pharm, Key Lab Trop Biol Resources, Minist Educ, Haikou 570228, Hainan, Peoples R China;[4]Tongji Univ, Shanghai Peoples Hosp 10, Clin Med Sci & Tech Innovat Ctr, Sch Med, Shanghai 200092, Peoples R China;[5]Dali Univ, Coll Pharm, Yunnan Key Lab Screening & Res Antipathogen Plant, Dali 671000, Peoples R China

年份：2022

卷号：13

期号：40

起止页码：11738

外文期刊名：CHEMICAL SCIENCE

收录：;EI(收录号：20224312991544);WOS:【SCI-EXPANDED(收录号:WOS:000859232000001)】；

基金：The authors are thankful for the.nancial support from the Natural Science Foundation of China (22037002, 22007032 and 21977082), the Natural Science Basic Research Program of Shaanxi (2020JC-38), the Innovation Program of Shanghai Municipal Education Commission (2021-01-07-00-02-E00104), the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (2021 Sci & Tech 03-28), the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212702), the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), the Chinese Postdoctoral Science Foundation, China (No. 2019M660083), the Postdoctoral Innovation Talent Support Program, China (No. BX20200131), and the Shanghai Sailing Program, China (No. 20YF1411200). Male and female ICR mice (8 weeks, weighing 20-24 g) were purchased from Zhejiang Vital River Laboratory Animal Technology Co., Ltd. and male C57BL/6 mice (7 weeks, weighing 20-22 g) were purchased from Shanghai Jiesijie Laboratory Animal Co., Ltd. All mice were maintained under controlled temperature (22-23 ~C) and light (12:12 hours of light-dark cycles) conditions at the animal center, approved by the Institutional Animal Care and Use Committees of Tongji University in compliance with Chinese law for experimental animals with an approval number of SYXK (Shanghai) 2020-0002.

语种：英文

外文关键词：Mammals

摘要：Selective elimination of senescent cells (senolysis) has become a promising therapeutic strategy for the management of chronic renal failure (CRF), but the senolytic molecular pathways towards CRF therapy are limited. Here, we present for the first time a senescence-associated beta-galactosidase (SA-beta-gal) activatable theragnostic prodrug strategy to pertinently and effectively treat CRF in mice with the aid of fluorescence-guided senolysis. The signs of premature senescence, including the overexpression of beta-gal, have been found in kidneys of mice with CRF, making this enzyme particularly suitable as a trigger of prodrugs for CRF therapy. With this unique design, our pioneering prodrug TSPD achieved the activation of a fluorophore for tracking and the specific release of the parent drug, gemcitabine, in beta-gal-enriched cells after activation with SA-beta-gal. In mice with CRF, abdominal administration of TSPD was effective for improvement of the kidney functions, supporting the feasibility of the SA-beta-gal-dependent senolysis therapy towards CRF.