The drug discovery and therapeutic nano-strategies targeting cellular senescence

Cellular senescence is a primary driver of aging, where damaged or senescent cells (SnCs) continuously accumulate in the body, altering the local tissue environment and causing various pathologies in different organs or tissues, offering brand-new diagnostic and therapeutic possibilities for aging-related disease. This review begins by discussing the multiple molecular mechanisms of cellular senescence. We mainly focus on the therapeutic strategies and their clinical applications targeting cellular senescence, where senolytic and senomorphic drugs are currently two main categories of anti-aging therapies. Besides, nicotinamide adenine dinucleotide (NAD⁺) enhancers or multiple therapies for anti-inflammatory and immunomodulation also hold great promise. Crucially, we highlight the design principles and formulation strategies on engineered nanotechnology-based drug delivery system (NDDS) targeting SnCs, including combination therapies and drug loading, delivery routes and bio-distribution, targeted therapy and precision medicine as well as stimuli-responsive drug release. Subsequently, we comprehensively analyze the therapeutic nano-strategies for neurodegenerative diseases, cardiovascular diseases, bone and joint diseases, fibrosis disease, cancer, and other aging-related diseases targeting cellular senescence. Finally, we propose the strength, weakness, opportunity and threat (SWOT) analysis and summarize the future development directions of the therapeutic nano-strategies targeting manipulating SnCs and treating aging related diseases, thereby paving the way for innovative and effective approaches for aging-related disease management.