New Ca2+ based anticancer nanomaterials trigger multiple cell death targeting Ca2+ homeostasis for cancer therapy

Calcium ion (Ca2+) is a necessary element for human and Ca2+ homeostasis plays important roles in various cellular process and functions. Recent reaches have targeted on inducing Ca2+ overload (both intracellular and transcellular) for tumor therapy. With the development of nanotechnology, nanoplatform-mediated Ca2+ overload has been safe theranostic model for cancer therapy, and defined a special calcium overload-induced tumor cell death as "calcicoptosis". However, the underlying mechanism of calcicoptosis in cancer cells remains further identification. In this review, we summarized multiple cell death types due to Ca2+ overload that induced by novel anticancer nanomaterials in tumor cells, including apoptosis, autophagy, pyroptosis, and ferroptosis. We reviewed the roles of these anticancer nanomaterials on Ca2+ homeostasis, including transcellular Ca2+ influx and efflux, and intracellular Ca2+ change in the cytosolic and organelles, and connection of Ca2+ overload with other metal ions. This review provides the knowledge of these nano-anticancer materials-triggered calcicoptosis accompanied with multiple cell death by regulating Ca2+ homeostasis, which could not only enhance their efficiency and specificity, but also enlighten to design new cancer therapeutic strategies and biomedical applications.