A nanozyme combining multi-enzymatic activity with targeted carbon monoxide delivery for synergistic antitumor therapy†

Chemodynamic therapy (CDT) has been emerging as a hot spot in tumor ablation treatment. However, CDT effectiveness is unavoidably hindered by insufficient hydrogen peroxide (H₂O₂) in the tumor microenvironment (TME). Therefore, developing a nanoplatform with the ability to self-supply H₂O₂ and enhance CDT antitumor efficacies remains a major challenge. In this work, a novel near infrared (NIR) light-responsive nanoplatform CuPO@PDA@MnCO@FA (abbreviated as CPMF) was prepared for precise cancer therapy, which is composed of polydopamine (PDA) wrapped copper phosphate (CuPO@PDA), a carbon monoxide (CO) donor (MnCO) and a targeting group of folic acid (FA). CPMF displayed target-accumulation in cancer cells with the self-enhanced catalytic activity of superoxide dismutase (SOD) and peroxidase (POD) that could convert superoxide anions (O₂˙⁻) into H₂O₂, and in turn amplify the Fenton-like reaction to induce stronger cytotoxic hydroxyl radicals (˙OH), showing excellent self-enhanced CDT performance. Furthermore, 808 nm NIR light irradiation could trigger the release of CO from the nanoplatform and produce an obvious photothermal effect in HeLa cells, showing admirable anticancer efficiency. The CPMF nanoplatform exhibited multimodal therapies (photothermal therapy, CDT and gas therapy) against HeLa cancer cells, which provides a novel paradigm for potential cancer clinical applications.