From Cold to Hot: Nanozyme-Based Strategies for Reprogramming the Tumour Immunoenvironment

The immunosuppressive tumour immune microenvironment (TIME) is a fundamental barrier that renders "cold" tumours resistant to conventional cancer immunotherapies. Nanozymes, catalytic nanomaterials with enzyme-mimicking activities, have emerged as powerful and versatile agents for reprogramming the TIME and igniting robust antitumour immunity. This review systematically elucidates how nanozymes, through their multi-enzyme catalytic properties, orchestrate a multifaceted attack on the immunosuppressive TIME by regulating reactive oxygen species, alleviating hypoxia, depleting antioxidants, and inducing immunogenic cell death, ferroptosis, and cuproptosis. These catalytic actions collectively promote dendritic cell maturation, enhance cytotoxic T lymphocyte infiltration, and repolarise tumour-associated macrophages toward an M1 phenotype, thereby effectively converting immunologically "cold" tumours into "hot" ones. Furthermore, we deeply analyse the synergistic potential of nanozymes when integrated with established therapies-including immune checkpoint blockade, phototherapy, sonodynamic therapy, chemotherapy, and radiotherapy. Finally, by discussing advanced bioengineered platforms and addressing the ongoing challenges related to biosafety and clinical translation, we envision that nanozyme-based catalytic immunoengineering represents a paradigm-shifting approach for next-generation combinatorial cancer immunotherapy.