Amplifying Ca overload by engineered biomaterials for synergistic cancer therapy.

Ca overload is one of the most widely causes of inducing apoptosis, pyroptosis, immunogenic cell death, autophagy, paraptosis, necroptosis, and calcification of tumor cells, and has become the most valuable therapeutic strategy in the field of cancer treatment. Nevertheless, several challenges remain in translating Ca overload-mediated therapeutic strategies into clinical applications, such as the precise control of Ca dynamics, specificity of Ca homeostasis dysregulation, as well as comprehensive mechanisms of Ca regulation. Given this, we comprehensively reviewed the Ca-driven intracellular signaling pathways and the application of Ca-based biomaterials (such as CaCO-, CaP-, CaO-, CaSi-, CaF-, and CaH-) in mediating cancer diagnosis, treatment, and immunotherapy. Meanwhile, the latest researches on Ca overload-mediated therapeutic strategies, as well as those combined with multiple-model therapies in mediating cancer immunotherapy are further highlighted. More importantly, the critical challenges and the future prospects of the Ca overload-mediated therapeutic strategies are also discussed. By consolidating recent findings and identifying future research directions, this review aimed to advance the field of oncology therapy and contribute to the development of more effective and targeted treatment modalities.