Smart Mitochondria‐Specific Anchored Gold‐based Nanosystem for Integration of Tumor Imaging and Treatment

Abstract Although recent advances have been made in improving the efficacy of photodynamic therapy, efficient therapeutic approaches based on reactive oxygen species (ROS) are needed, particularly mitochondria‐specific targeting of nanomaterials that can alter the internal environment of organelles. Herein, we report the facile synthesis of mitochondria‐specific anchored nano‐complexes (AG‐C_NP) comprised of a skeleton of gold and carbon atoms for cancer therapy. Compared to the effects of gold nanoclusters (Au NCs), AG‐C_NP shows enhanced fluorescence imaging effects, which can be used for tumor monitoring. AG‐C_NP targets the mitochondria and increases ROS damage in cancer cells. After treatment with AG‐C_NP, the tumor inhibition rate reaches 70.94%, which is 25.98% and 36.91% higher than that of free doxorubicin (DOX) and gemcitabine (Gem), respectively. Studying the mechanism of AG‐C_NP inhibiting cancer shows that AG‐C_NP can promote tumor cells to produce excessive ROS by overexpressing P53 and increasing the number of apoptotic cancer cells, which is caused by overexpression of Caspase1 that was closely related to cell apoptosis. AG‐C_NP is a promising anticancer drug that targets the mitochondria in vivo to trigger excessive ROS production in tumor cells and inhibit tumor growth.