Mitochondria-Targeted\nGold Biometallization for Photoacoustically\nVisualized Photothermal Cancer Therapy

Subcellular biomineralization systems with cellular intervention\nfunctions have shown great potential in cancer theranostic applications.\nHowever, the lack of subcellular specificity, high ion concentrations,\nand long incubation time required for biomineralization still limit\nits <i>in vivo</i> therapeutic efficacy. Herein, we report\na mitochondria-targeted polymer–gold complex (TPPM-Au) to realize\nmitochondrial biometallization, which involves analogous mechanisms\nduring biomineralization, for cancer treatment <i>in vivo</i>. The TPP-containing TPPM-Au delivered more Au<sup>3+</sup> selectively\ninto the mitochondria of cancer cells than normal cells, rapidly mineralizing\nto gold nanoparticles (GNPs) and consuming a large amount of the antioxidant\nglutathione (GSH). The formed GNPs can further continue consuming\nGSH with the atomic economy by forming Au–S with GSH, which\nfurther results in the accumulation of reactive oxygen species (ROS),\nthereby impairing mitochondrial function and inducing cell apoptosis.\nMore importantly, TPPM-Au is capable of having superior tumor-penetrating,\nexcellent photothermal and photoacoustic properties, endowing it with\nthe ability to inhibit tumor growth through spatiotemporally monitorable\nmitochondria-targeted biometallization and photothermal therapy. The\nmitochondria-targeted gold biometallization theranostic platform provides\ninsight into the application of subcellularly targeted biometallization\nor biomineralization in cancer therapy.