Near-Infrared Zn-Doped Cu2S Quantum Dots: An Ultrasmall Theranostic Agent for Tumor Cell Imaging and Chemodynamic Therapy

Theranostic agents that integrated chemodynamic therapy (CDT) and imaging functions have great potential application in personalized cancer therapy. However, most theranostic agents were fabricated by chemically coupling two or more independent functional units with diagnostic or therapeutic capabilities, and therefore have a large size. To date, one-step synthesis of unmodified ultrasmall quantum dots (QDs) integrating CDT and fluorescence imaging capabilities remains a challenge. Herein, we reported a simple one-step synthesis method of ultrasmall (2.46 nm) Zn-doped Cu2S (Zn:Cu2S) QDs with inherent properties of both high CDT activity and near-infrared fluorescence imaging capability. The fluorescence of Cu2S QDs was significantly enhanced approximately tenfold after Zn doping due to the compensation of defects. In vitro and in vivo experiments demonstrated that the Zn:Cu2S QDs could specifically and significantly inhibit the cancer cell growth (inhibition rate exceeded 65%) without damaging the normal cells. Furthermore, the CDT mechanism study suggested that a Fenton-like reaction occurred after the Zn:Cu2S QDs entered the tumor cells, inducing apoptosis via the mitochondrial signaling pathway, and activating the production of reactive oxygen species (ROS) and autophagy to selectively eliminate tumor cells to achieve CDT. This work proposed a simple one-step synthesis of unmodified ultrasmall QDs with fluorescence imaging and CDT, which provides a promising strategy for QDs to act as multi-functional theranostic agents.