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

Abstract Calcium ion (Ca 2+ ), 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 (CaCl 2 ) into cancer cells and thereby triggering cell death upon near‐infrared (NIR) irradiation is demonstrated. In the absence of NIR irradiation, the nanosystem, denoted CaCl 2 ‐PCM‐AuNC, shows negligible cytotoxicity because the Ca 2+ ions are fully encapsulated in a solid matrix. Upon NIR irradiation, the Ca 2+ ions are swiftly released due to the melting of PCM matrix in response to photothermal heating. The sudden increase in intracellular Ca 2+ causes disruption to the mitochondrial Ca 2+ 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.