Ion overload-induced pyroptosis in nanoscale systems: A novel strategy for tumor immunotherapy

Pyroptosis is recognized as a form of programmed cell death that can trigger inflammatory responses and activate the immune system. Although implicated in the pathogenesis of various diseases, it has emerged as a potent strategy in tumor immunotherapy. Ion overload has been considered as a promising approach in cancer therapy by disrupting intracellular ions homeostasis, inducing organelle damage and impairing metabolic pathways. While several published reviews have mentioned ion overload as a trigger of various forms of cell death, a comprehensive and up-to-date synthesis specifically focusing on pyroptosis and the related nanomaterial design strategies has been lacking. Herein, we detail the historical discovery and characteristics of pyroptosis. Then, we summarize the molecular mechanisms underlying pyroptosis and its interplay with anti-tumor immunity. Finally, the reports on pyroptosis induced by ion overload, such as Ca 2+ ions, Zn 2+ ions, Cu 2+ ions, Na + ions, etc. are also highlighted. Currently, ion-overload-induced pyroptosis faces a series of challenges and opportunities. Deepening the understanding of the relationship between ion-overload and pyroptosis, and then fully leveraging their advantages while effectively addressing corresponding issues are crucial for the advancement of nanomedicine and tumor treatment.