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 <i>in situ</i> hyaluronic acid capping endows the nanodots with efficient and highly selective uptake in breast cancer cells both <i>in vitro</i> and <i>in vivo</i>. 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.