A Self-Assembling Senolytic Prodrug with Enhanced Bioavailability and Selective Activation for Targeting Senescent Retinal Pigment Epithelium.

ABSTRACT: Senolytic therapy, which targets and selectively eliminates senescent cells, has emerged as a promising strategy for treating various age-related diseases. However, its clinical application is often limited by poor bioavailability, off-target toxicity, and the need for invasive administration routes. To overcome these challenges, we developed N201-gal, a novel β-galactosidase-reactive senolytic prodrug that self-assembles into stable nanoparticles, enabling oral administration and improved systemic bioavailability. Once internalized by senescent cells, N201-gal responds to β-galactosidase overexpression, triggering controlled drug release and inducing selective apoptosis in senescent cells while sparing normal cells. The nanoparticle formulation exhibited favorable physicochemical properti

SUBMITTER: Ok H 

PROVIDER: S-EPMC12484856 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature