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Near‐Infrared‐Triggered Release of Ca2+ Ions for Potential Application in Combination Cancer Therapy

Calcium ion (Ca2+), an abundant species in the body, is a potential therapeutic ion with manageable side effects. However, the delivery of such a highly charged species represents a great challenge. Here, a nanosystem based on Au nanocages (AuNCs) and a phase‐change material (PCM) for delivering calcium chloride (CaCl2) into cancer cells and thereby triggering cell death upon near‐infrared (NIR) irradiation is demonstrated. In the absence of NIR irradiation, the nanosystem, denoted CaCl2‐PCM‐AuNC, shows negligible cytotoxicity because the Ca2+ ions are fully encapsulated in a solid matrix. Upon NIR irradiation, the Ca2+ ions are swiftly released due to the melting of PCM matrix in response to photothermal heating. The sudden increase in intracellular Ca2+ causes disruption to the mitochondrial Ca2+ homeostasis and thus the loss of mitochondrial membrane potential, subsequently resulting in cell apoptosis. This nanosystem provides a new method for cancer treatment by tightly managing the intracellular concentration of a physiologically essential element.