Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.

The effectiveness of cancer immunotherapy is often compromised by a highly immunosuppressive tumor microenvironment (TME), characterized by pro-tumorigenic metabolic abnormalities including hypoxia, nutrient competition, and accumulation of toxic metabolites. Here, we review the potential of nanozymes to directly modulate immunometabolic pathways to empower immunotherapeutic efficacy. We describe how nanozymes with distinct catalytic properties can reprogram the TME to alleviate hypoxia, supplement nutrients, and eliminate immunosuppressive metabolites such as glutathione and kynurenine. The nanozyme-enabled biocatalytic remodeling of tumor immunometabolic landscape enhances the function and maturation of antigen-presenting cells (APCs) while blocking immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), leading to the restoration of metabolic fitness of antitumorigenic T cells. Furthermore, we explore the synergy of nanozymes with established immunotherapeutics such as immune checkpoint inhibitors (ICB), adoptive cell therapies, and cancer vaccines. Finally, we address the challenges of translating these findings into clinical practice and propose future directions for integrating these nanozyme-based strategies into innovative combination therapies.