Regulation of Ca2+ for Cancer Cell Apoptosis through Photothermal Conjugated Nanoparticles

Ca²⁺ overload is caused by the abnormal accumulation of Ca²⁺, which is a potential therapeutic strategy for inhibiting tumor growth. However, due to the limited intracellular Ca²⁺ concentration, its anticancer effect is non-significant. Herein, near-infrared (NIR)-responsive nanoparticles NPs-PCa (DPPC-DSPE-PEG2000-NH₂@PDPP@CaO₂@DOX) were designed and prepared to achieve photothermal trigger of Ca²⁺ release, thereby increasing intracellular Ca²⁺ content. Furthermore, the nanoparticles convert light to heat to activate the transient receptor potential cation channel subfamily V member 1 (TRPV1) ion channels, allowing external Ca²⁺ to flow into the cells, further increasing the Ca²⁺ concentration. NPs-PCa nanoparticles overcome the limitation of insufficient concentration by increasing Ca²⁺ in both internal and external approaches. Meanwhile, an imbalance of intracellular Ca²⁺ induces mitochondrial dysfunction and ultimately results in cancer cell death. This study provides an effective strategy for inhibiting breast cancer tumor growth by regulating Ca²⁺ concentration.