Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy

Abstract Calcium ions (Ca 2+ ) are indispensable and versatile metal ions that play a pivotal role in regulating cell metabolism, encompassing cell survival, proliferation, migration, and gene expression. Aberrant Ca 2+ levels are frequently linked to cell dysfunction and a variety of pathological conditions. Therefore, it is essential to maintain Ca 2+ homeostasis to coordinate body function. Disrupting the balance of Ca 2+ levels has emerged as a potential therapeutic strategy for various diseases, and there has been extensive research on integrating this approach into nanoplatforms. In this review, the current nanoplatforms that regulate Ca 2+ homeostasis for cancer therapy are first discussed, including both direct and indirect approaches to manage Ca 2+ overload or inhibit Ca 2+ signalling. Then, the applications of these nanoplatforms in targeting different cells to regulate their Ca 2+ homeostasis for achieving therapeutic effects in cancer treatment are systematically introduced, including tumour cells and immune cells. Finally, perspectives on the further development of nanoplatforms for regulating Ca 2+ homeostasis, identifying scientific limitations and future directions for exploitation are offered.