Calcium-free nanomaterials-mediated calcium overloading for cancer therapy

• • Calcium-free nanomaterials avoid off-target Ca2+ release, mitigating hypercalcemia and cardiac/renal toxicity associated with exogenous calcium salts (e.g., CaCO3, CaO2). • • These platforms precisely regulate endogenous Ca2+ channels (e.g., TRPV1) and pumps (e.g., PMCA, SERCA) to induce calcium overload, achieving targeted tumor therapy. • • The strategy triggers mitochondrial dysfunction, ER stress, and immunogenic cell death, enhancing antitumor immunity and inhibiting metastasis. • • Design principles include activation of calcium channels (e.g., via capsaicin) or inhibition of efflux pumps, with demonstrated efficacy in combination therapies (e.g., photodynamic therapy).