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

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 Ca2+ level exceeds the tolerance of cells (called Ca2+ overload), oxidative stress, mitochondrial damage, and cell/mitochondria apoptosis happen. Therefore, Ca2+ 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 Ca2+-based nanomaterials (such as Ca-3(PO4)(2), CaCO3, CaO2, CaH2, CaS, and others) able to trigger intracellular Ca2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca2+-based nanomaterials and the different types of strategies to enhance Ca2+ overload are discussed in detail. Moreover, the design of more efficient Ca2+ 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 Ca2+ release from nanomaterials by increasing the intracellular H+ level and by photothermal effect, and 3) the overload maintenance by Ca2+ efflux inhibition, Ca2+ influx promotion, or promoting Ca2+ release from the endoplasmic reticulum.