Recent Advances in Calcium‐Based Anticancer Nanomaterials Exploiting Calcium Overload to Trigger Cell Apoptosis

Abstract Calcium ion is vital for the regulation of many cellular functions and serves as a second messenger in the signal transduction pathways. Once the intracellular Ca 2+ level exceeds the tolerance of cells (called Ca 2+ overload), oxidative stress, mitochondrial damage, and cell/mitochondria apoptosis happen. Therefore, Ca 2+ overload has started to be deeply exploited as a new strategy for cancer therapy due to its high efficiency and satisfactory safety. This review aims to highlight the recent development of Ca 2+ ‐based nanomaterials (such as Ca 3 (PO 4 ) 2 , CaCO 3 , CaO 2 , CaH 2 , CaS, and others) able to trigger intracellular Ca 2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca 2+ ‐based nanomaterials and the different types of strategies to enhance Ca 2+ overload are discussed in detail. Moreover, the design of more efficient Ca 2+ overload‐mediated cancer therapies is prospected mainly based on 1) the enhanced cellular uptake by surface modification and morphology optimization of nanomaterials, 2) the accelerated Ca 2+ release from nanomaterials by increasing the intracellular H + level and by photothermal effect, and 3) the overload maintenance by Ca 2+ efflux inhibition, Ca 2+ influx promotion, or promoting Ca 2+ release from the endoplasmic reticulum.