New Ca based anticancer nanomaterials trigger multiple cell death targeting Ca homeostasis for cancer therapy.

Calcium ion (Ca) is a necessary element for human and Ca homeostasis plays important roles in various cellular process and functions. Recent reaches have targeted on inducing Ca overload (both intracellular and transcellular) for tumor therapy. With the development of nanotechnology, nanoplatform-mediated Ca 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 Ca 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 Ca homeostasis, including transcellular Ca influx and efflux, and intracellular Ca change in the cytosolic and organelles, and connection of Ca overload with other metal ions. This review provides the knowledge of these nano-anticancer materials-triggered calcicoptosis accompanied with multiple cell death by regulating Ca homeostasis, which could not only enhance their efficiency and specificity, but also enlighten to design new cancer therapeutic strategies and biomedical applications.