文献类型：期刊文献

英文题名：Molecular engineering development of β-galactosidase-activatable fluorogenic probes for precise senescence tracking in cells, tissues and a mouse model of psoriasis

作者：Lv, Xinhang[1,2];Yu, Yangxin[1,2];Chen, Zhuowei[1,2];Wang, Guangwei[3];Li, Xiaokang[4];Sun, Ling[1,2];Wu, Lingyu[1,2];Wu, Jiale[1,2];Li, Jian[1,2,4,5];Guo, Yuan[3];Shi, Donglei[1,2]

机构：[1]Hainan Univ, Sch Pharmaceut Sci, Key Lab Trop Biol Resources, Minist Educ, Haikou 570228, Hainan, Peoples R China;[2]Hainan Univ, Hainan Engn Res Ctr Drug Screening & Evaluat, Sch Pharmaceut Sci, Haikou 570228, Hainan, Peoples R China;[3]Northwest Univ, Engn Res Ctr Western Resource Innovat Med Green Mf, Sch Chem Engn, Minist Educ, Xian 710127, Peoples R China;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn,Shanghai Frontiers S, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai Key Lab New Drug Design,Sch Pharm, Shanghai 200237, Peoples R China;[5]Shihezi Univ, Sch Pharm, Key Lab Xinjiang Phytomed Resource & Utilizat, Minist Educ, Shihezi 832003, Peoples R China

年份：2025

卷号：444

外文期刊名：SENSORS AND ACTUATORS B-CHEMICAL

收录：;EI(收录号：20250252953);WOS:【SCI-EXPANDED(收录号:WOS:001544363900001)】；

基金：The authors gratefully appreciate the financial support from the National Natural Science Foundation of China (grants 22037002 to J.L. and Y.G., 22477101 to Y.G., 32121005 to J.L., 22407038 to D.S.) , the Innovation Program of Shanghai Municipal Education Commission (grant 2021 01 07 00 02 E00104 to J.L.) , the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (grant 2021 Sci & Tech 03-28 to J.L.) , the Innovative Research Team of High-level Local Universities in Shanghai (grant SHSMU-ZDCX20212702 to J. L.) , the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering (2060204 to J.L.) and the Hainan Provincial Natural Sci-ence Foundation of China (825MS073 to D.S.) . The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

语种：英文

外文关键词：SA-beta-gal; Senescent cells; Psoriasis; Fluorescent probe; Anti-aging drugs; High-throughput evaluation

摘要：Senescent cells, which play a pivotal role in aging and age-related diseases, have been identified as a critical "target" for interventions aimed at decelerating aging. However, recognition tools of this target for evaluating anti-aging drugs are limited, leading the use of animal lifespan phenotypes for screening and evaluating these therapeutics, a process that is both time-consuming and labor-intensive. To this end, we conducted engineering research on fluorescent probes and developed the pioneering probe for monitoring senescent cells based on senescence-associated (3-galactosidase (SA-(3-gal), facilitating the assessment of senescence and further evaluating the effectiveness of anti-aging therapeutics. The proposed molecular engineering strategy of such probes, involving multi-stage structure optimization and properties requirements were applied to develop candidate molecules, including TZ0805 to TZ0813A. Following multiple rounds of structural modifications, TZ0813A was developed as the pioneering probe. The probe effectively monitored SA-(3-gal in different senescent cell models, including ROS-induced or doxorubicin-induced senescence, as well as replication-induced senescence. Additionally, a visual high-throughput screening of 28 kinds of drugs were performed using TZ0813A by assessing the expression level of SA-(3-gal. Moreover, TZ0813A successfully visualized senescent cells in the kidney sections of naturally aged mice and doxorubicin-induced aged mice and assessed the anti-aging effects of metformin in doxorubicin-induced aged mice. Furthermore, utilizing TZ0813A, we have achieved the visualization of senescent cells at lesion site of psoriatic model mice in vivo. Our results demonstrate TZ0813A is valuable in high-throughput evaluation of anti-aging drugs and tracking senescence.