One-Pot Synthesis of Tumor-Targeted Gold-Doped Cu_1.92S Plasmonic Nanodots for Enhanced NIR-Triggered, pH-Responsive PTT/PDT/CDT

Copper-based sulfides are attractive candidates for NIR I and II responsive photothermal therapy but often suffer from high hydrophobicity, suboptimal photothermal conversion, and poor biostability and biocompatibility. In the present work, a rapid, one-pot synthesis method was developed to obtain Au-doped Cu_1.92S (ACSH NDs) dual plasmonic nanodots. ACSH NDs exhibit excellent peroxidase-like catalytic activity for pH-responsive ^•OH radical generation along with efficient glutathione depletion under tumor microenvironment mimicking conditions. Upon exposure to NIR-I laser light, ACSH NDs demonstrate high photothermal conversion efficiency of 47.44% as well as significant photodynamic effect through singlet oxygen generation. The in situ hyaluronic acid capping endows the nanodots with efficient and highly selective uptake in breast cancer cells both in vitro and in vivo. Simultaneous chemodynamic and NIR-triggered photothermal/photodynamic activities of ACSH NDs result in synergistic tumor cell death with 98% tumor inhibition in a single-dose mouse model study. Therefore, the developed ACSH NDs show remarkable potential for single nanoplatform-actuated drug-free multimodal cancer therapy.