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.