A Covalent Organic Framework Derived N‑doped Carbon Nanozyme as the All-rounder for Targeted Catalytic Therapy and NIR-II Photothermal Therapy of Cancer

Nanomaterials with intrinsic enzyme-like activities (nanozymes) have gained significant attention in cancer catalytic therapy; however, developing metal-free nanozymes with multivariant enzyme-like activity as the “all-rounder” for cancer therapy remains challenging. Herein, a covalent organic framework (COF) derived carbon-based nanozyme is rationally devised to achieve synergistic catalytic therapy and second near-infrared (NIR-II) photothermal therapy of cancer. The developed nanozyme possesses multivariant enzyme-like activities, including oxidase (OXD)-like, catalase (CAT)-like, and peroxidase (POD)-like catalytic activities, which enables the nanozyme to produce adequate reactive oxygen species (ROS) for cancer cell killing. Furthermore, the nanozyme showed excellent photothermal converting activity that could kill cancer cells upon NIR-II laser irradiation, owing to the strong NIR-II absorption capacity of carbon-based materials. It is also worth noting that the nanozyme exhibited cytotoxicity specifically in tumor tissue profiting from the discrepant H₂O₂ level between tumor and normal tissue and the spatiotemporal controllability of laser irradiation. This work may inspire further development of intelligent nanozymes in biological applications across broad therapeutic and biomedical fields.