Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy

Cellular senescence, a hallmark of aging, entails the irreversible cessation of cell division in response to intrinsic and extrinsic stressors. Though metabolically active, senescent cells lose their replicative capacity and resist apoptotic signals, accumulating tissues with advancing age and contributing to age-related pathologies. Senescence is characterized by the acquisition of a senescence-associated secretory phenotype (SASP), releasing a myriad of bioactive molecules. SASP not only influences intracellular processes but also orchestrates the modification of neighboring cells and the surrounding microenvironment. In the context of aging, the proportion of senescent cells escalates, ranging from 1 to 15% in different species, tissues, and activity levels. This accumulation is associated with age-related diseases and morbidity. Beyond aging, senescence induction is observed in response to cancer treatments, including radiotherapy and chemotherapy, potentially contributing to cancer metastasis and recurrence. Consequently, the exploration of senolytic therapies aimed at eliminating senescent cells has gained considerable momentum. Addressing the limitations of free therapeutics, nano-drug delivery systems have been meticulously engineered to enhance solubility, stability, and targeted delivery. These nanocarriers overcome challenges related to poor bioavailability, uncontrolled biodistribution, and off-target effects, thereby improving therapeutic efficacy and safety. Precise control over nanoparticle size and uniformity enables targeted distribution, enhancing therapeutic precision. While nanomedicine is revolutionizing healthcare, its potential to mitigate cellular senescence remains largely unexplored despite extensive cancer research. This comprehensive review aims to consolidate the current understanding of cellular senescence and its pathological consequences. Furthermore, we present an in-depth analysis of studies employing nano-drug delivery systems in cellular senescence research, emphasizing their potential role and prospects in this evolving scientific landscape. This research is a significant step towards filling this gap and paving the way for future advancements in the field.