Precisely Designed Calcium-Based Nanomaterials: From Regulation of Cellular Ca²⁺ Homeostasis to Cancer Therapy

Intracellular calcium ion (Ca2+) homeostasis is closely associated with the maintenance of cellular functions and even influences the process of cellular fate. Particularly, Ca2+ homeostasis directly or indirectly participates in various methods of tumor occurrence and development, including proliferation, migration, and apoptosis of tumor cells. Considering the advancements in strategies for cancer therapy based on disrupting Ca2+ homeostasis, this article provides a comprehensive review from the perspective of the relationship between Ca2+ homeostasis and tumor therapy, focusing on the common Ca2+-based nanomaterials and self-regulatory mechanisms of Ca2+ homeostasis toward diagnostic and therapeutic applications. Notably, the disruption of Ca2+ homeostasis provides exceptional possibilities for the design of Ca2+-based nanomaterials through various pathways, such as inducing Ca2+ overload to directly kill tumor cells, indirectly inhibiting tumor growth by affecting various tumor microenvironments, and promoting calcification phenomena for bioimaging in tumor diagnosis. Finally, we summarize the article with a perspective, exploring limitations and challenges in applying Ca2+-based materials mediated by disrupting Ca2+ homeostasis and providing prospects for their clinical development.