A senolysis-based theragnostic prodrug strategy towards chronic renal failure.

ABSTRACT: 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, gem

SUBMITTER: Song Y 

PROVIDER: S-EPMC9580481 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature