Mitochondria-Targeted Gold Biometallization for Photoacoustically Visualized Photothermal Cancer Therapy

Subcellular biomineralization systems with cellular intervention functions have shown great potential in cancer theranostic applications. However, the lack of subcellular specificity, high ion concentrations, and long incubation time required for biomineralization still limit its in vivo therapeutic efficacy. Herein, we report a mitochondria-targeted polymer–gold complex (TPPM-Au) to realize mitochondrial biometallization, which involves analogous mechanisms during biomineralization, for cancer treatment in vivo. The TPP-containing TPPM-Au delivered more Au³⁺ selectively into the mitochondria of cancer cells than normal cells, rapidly mineralizing to gold nanoparticles (GNPs) and consuming a large amount of the antioxidant glutathione (GSH). The formed GNPs can further continue consuming GSH with the atomic economy by forming Au–S with GSH, which further results in the accumulation of reactive oxygen species (ROS), thereby impairing mitochondrial function and inducing cell apoptosis. More importantly, TPPM-Au is capable of having superior tumor-penetrating, excellent photothermal and photoacoustic properties, endowing it with the ability to inhibit tumor growth through spatiotemporally monitorable mitochondria-targeted biometallization and photothermal therapy. The mitochondria-targeted gold biometallization theranostic platform provides insight into the application of subcellularly targeted biometallization or biomineralization in cancer therapy.