Nanozyme-driven closed-loop regulation of antitumor immunity: From catalytic reprogramming to immunological synergy

Cancer remains a formidable global public health burden, with an estimated 2.0 million incident cases and 618,000 deaths anticipated in 2025. Despite the broad clinical deployment of surgery, radiotherapy, chemotherapy and immunotherapy, tumor remains plagued by recurrence and metastasis. Nanozymes, emerging as potent tools in oncology, mimic natural enzymes with high catalytic stability and can synergize with photothermal therapy, photodynamic therapy, chemodynamic therapy, and other modalities to effectively eradicate tumors. This review focuses on nanozyme-based immunotherapy and proposes a novel “closed-loop regulatory” strategy. By leveraging the multi-enzyme activities and stimuli-responsiveness of nanozymes, dynamically senses the tumor microenvironment for recognition, implements catalytic interventions, and establishes self-amplifying feedback loops via immune activation or metabolic remodeling. This closed-loop system eliminates immunosuppressive signals while enhancing pro-immunity, thereby overcoming the limitations of linear therapies and enabling sustained efficacy amplification. Despite its promise, challenges including long-term biosafety, targeted delivery, and manufacturing scalability require further resolution.