Dual-Responsive Cu(I) and Cu(II) Co-Doped Carbon Dots for Synergistic Chemodynamic-Photothermal Antitumor Therapy

Multifunctional nanoplatforms have shown great promise in cancer therapy. However, their efficacy is limited by the low specificity and the tumor microenvironment (TME). Many functional organic acids, such as folic acid and gallic acid, have shown important potential in the research of antitumor drugs. Herein, we report the preparation of the biocompatible theranostic carbon dots (FG@Cu-CDs) with folic acid, gallic acid, and CuSO4 as the precursors to realize the TME and near-infrared photothermal dual response. Cu(II) of FG@Cu-CDs is sensitive to glutathione (GSH) in the TME, which reduced the consumption of ·OH by glutathione (GSH). Cu(I) in FG@Cu-CDs could treat cancer by chemodynamic therapy (CDT) through a Fenton-like reaction. Moreover, FG@Cu-CDs could ablate tumors through photothermal therapy (PTT), which also has a positive effect on promoting CDT and depleting GSH. Based on the facts that CDT/PTT could enhance host immunogenicity, we used an immune checkpoint blocker, anti-PD-L1 antibody (αPD-L1), to boost tumor immunotherapy. This work opens up the possibility for multifunctional organic-acid-derived carbon dots combined with immune checkpoint blockers in cancer immunotherapy.