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

A nanosystem based upon gold nanocages and phase‐change materials is developed for controlling the intracellular release of Ca²⁺ ions through NIR laser irradiation. This new system can serve as an alternative to the traditional chemotherapeutics for cancer therapy with potentially reduced adverse impacts and side effects.

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.

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