Delivery Strategies Targeting Senescent Cells: From Precise Elimination to Functional Remodeling

This is the authors' abstract. We don't add key points for this paper.

The accumulation of senescent cells in tissues serves as a fundamental driver of aging and age-related pathologies, including chronic inflammation, tissue dysfunction, and organ degeneration. Conventional anti-aging interventions often suffer from limited specificity and off-target toxicity. Currently, developing therapeutic strategies capable of precisely targeting senescent cells is urgent. This review focuses on recent advances in delivery strategies designed to achieve either the selective elimination or functional modulation of senescent cells, with the goal of transitioning from broad-spectrum interventions to precision senotherapy. We systematically discuss the latest developments in senescence-targeting delivery platforms. To realize in vivo senescent-cell clearance, nanocarrier-based systems which are responsive to the senescent microenvironment and immune cell-based approaches are engineered. In parallel, we also reviewed emerging strategies for functional remodeling. Advanced delivery vehicles including lipid nanoparticles, extracellular vesicles, and engineered cell therapies are used to realize metabolic reprogramming and epigenetic modulation. The critical mechanisms of delivery systems in overcoming diverse barriers to improve specificity, bioavailability, and safety are highlighted. In this review, we aim to provide a preliminary framework that could serve as a useful reference for guiding the clinical translation of emerging senotherapies.