Cellular senescence is a state of cell cycle arrest caused by various types of stress, and it is characterized by morphological changes, metabolic reprogramming, and the release of the senescence-associated secretory phenotype (SASP). In cancer therapy, senescence plays a complex role by inhibiting cancer progression, mediating metabolic imbalance, modulating local immune responses, and restructuring the cancer microenvironment. These mechanisms have been harnessed to develop nano-drug delivery systems (Nano-DDSs)-based combination therapies for cancer. We systematically explain key biological features of cellular senescence and detail recent advances in creating drug delivery systems aimed at targeting cancer senescence through these four mechanisms. Additionally, we discuss the clinical challenges in translating senescence-targeting strategies with Nano-DDSs and propose future directions within an interdisciplinary framework. This review offers valuable insights into designing advanced Nano-DDSs based on the multidimensional regulatory mechanisms of cellular senescence and their application in cancer treatment.

Cellular senescence  /  Cancer therapy  /  Drug delivery systems  /  Senescence-associated secretory phenotype  /  Nanoplatforms  /  Tumor microenvironment  /  Senotherapy  /  Senolytics