Lipoic Acid CappedAg₂S Quantum Dots forMitochondria-Targeted NIR-II Fluorescence/Photoacoustic Imaging andChemotherapy/Photothermal Treatment of Tumors

Subcellular targeted therapy has recently emerged as a significant approach in cancer treatment. Mitochondria, as crucial organelles that not only provide cellular energy but also play roles in cell differentiation, signal transmission, reactive oxygen species production, apoptosis, and calcium homeostasis, are considered potential targets for cancer therapy. Silver sulfide quantum dots (Ag₂S QDs) have demonstrated exceptional capabilities in near-infrared fluorescence and photoacoustic imaging as well as photothermal treatment. Therefore, the development of Ag₂S QDs with mitochondrial-targeting ability is of particular significance. Herein, we developed a simple method for synthesizing aqueous-phase Ag₂S QDs using lipoic acid, an enzymatic substrate involved in cellular respiration, as a ligand and mitochondrial-targeting molecule. These Ag₂S QDs, which exhibit excellent water solubility and biocompatibility, can be produced in a single step and act as a mitochondrial-targeted theranostics. By adsorbing doxorubicin (DOX), we successfully created multifunctional nanoprobes called Ag₂S-DOX. In vitro and in vivo experiments demonstrated that Ag₂S-DOX was suitable for fluorescence and photoacoustic dual-mode imaging as well as synergistic mitochondrial-targeted chemotherapy and photothermal treatment, offering a promising strategy for tumor therapy.