NIR-II emitting fluorine-doped carbon dots with multi-enzyme mimic activities for NIR-II imaging and photothermal-enhanced cancer catalytic immunotherapy

Catalytic immunotherapy represents a promising approach to mitigate tumor metastasis and recurrence. The exploration of various advanced catalytic materials is opening new avenues for enhancing this therapy. However, metal-free carbon dot nanozymes with both NIR-II emission and NIR photoactivity are currently rare. Here, we report a metal-free multifunctional nanozyme, F-doped CDs (F-CDs) nanozyme, which exhibits a high NIR-II quantum yield and NIR-I photothermal effect for cancer catalytic immunotherapy. The F-CDs nanozyme demonstrated triplezyme-mimicking catalytic activity, including peroxidase (POD), glutathione peroxidase (GSH-px), and glucose oxidase (Gox). After modification with PEG, F-CDs@PEG exhibited excellent NIR-II bioimaging in vivo, comparable to FDA-approved dye indocyanine green (ICG). Under NIR laser irradiation, the remarkably enhanced catalytic activity of F-CDs@PEG disrupts the energy metabolism and redox balance of tumor cells, triggering intense tumor immunotherapy and reshaping the tumor immune microenvironment (TIME). Interestingly, we found that F-CDs@PEG can suppress immunosuppressive myeloid-derived suppressor cells (MDSCs) and alleviate T-cell exhaustion, leading to enhanced tumor growth inhibition and reduced splenomegaly. Importantly, F-CDs@PEG-mediated photothermal-enhanced catalytic immunotherapy can induce robust immune memory, offering long-term protection against tumor recurrence. Overall, the success of this study offers a feasible strategy for the future design and exploration of NIR-II CD-based nanozymes and metal-free nanocatalysts for catalytic immunotherapy.