Nano-modulators with the function of disrupting mitochondrial Ca(2+) homeostasis and photothermal conversion for synergistic breast cancer therapy

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca(2+) overload have attracted extensive attention. However, various limitations of current Ca(2+) nanogenerators make it difficult to maintain effective Ca(2+) overload concentrations. Here, we constructed a multimodal Ca(2+) nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca(2+) overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO(3)) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca(2+) nano-regulator SA/Cur@CaCO(3)-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca(2+) at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO(3), but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca(2+) nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02220-7.