Calcium-based nanotechnology for cancer therapy

Ions are the cornerstones of various biological functions and have been widely used for tumor therapy, called ion interference therapy (IIT). Calcium ion (Ca2+) is one of the most versatile signaling molecules, and as a second messenger, it regulates various physiological activities of normal cells and is intimately involved in the formation, proliferation, and migration of tumor cells. Meanwhile, Ca2+ also plays an important role in the differentiation, maturation, and migration of immune cells. Therefore, interfering with Ca2+ homeostasis to activate immune cells or induce tumor cell death through nanotechnology has become an effective way for tumor therapy. In this review, we (1) outline Ca2+ channels in cell membrane, endoplasmic reticulum (ER), mitochondria and lysosomes; (2) describe the underlying mechanisms of Ca2+-based tumor therapy by focusing on Ca2+-mediated immunotherapy, cellular Ca2+ overload, disrupted intracellular communication, and mitochondrial Ca2+ overload; (3) highlight recent advances in tumor therapy targeting Ca2+ signaling. This article provides new insights into calcium-based nanotechnology for cancer therapy.