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

Abstract

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.