biostudies-literatureUnknown13(40)Song YSelective 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 β-galactosidase (SA-β-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 β-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, gemChemical science11738-11745https://www.ebi.ac.uk/biostudies/studies/S-EPMC9580481biostudies-literatureA senolysis-based theragnostic prodrug strategy towards chronic renal failure.PMC9580481Li XLi JQiao SGuo YSun TShi DChen XSong YLiu WfalseA senolysis-based theragnostic prodrug strategy towards chronic renal failure.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 β-galactosidase (SA-β-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 β-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, gem2022-01-01T00:00:00Z2022 Oct2025-04-05T13:27:42.683Z2025-04-05T13:27:42.683ZS-EPMC95804813632091210.1039/d2sc03525a