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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunology

Background:

• The immunosuppressive tumor immune microenvironment (TIME) hinders conventional cancer immunotherapies, particularly for
• cold
• tumors.
• Nanozymes, nanomaterials with enzyme-mimicking catalytic activities, offer a novel strategy to overcome this barrier.

Purpose of the Study:

• To systematically review how nanozymes reprogram the TIME and enhance anti-tumor immunity.
• To elucidate the multifaceted attack mechanisms of nanozymes on the immunosuppressive TIME.
• To analyze the synergistic potential of nanozymes with existing cancer therapies.

Main Methods:

• Review of literature on nanozymes in cancer immunotherapy.
• Analysis of nanozyme catalytic properties and their effects on TIME components (ROS, hypoxia, antioxidants).
• Evaluation of nanozyme-induced cell death pathways (immunogenic cell death, ferroptosis, cuproptosis) and immune cell modulation (DC maturation, CTL infiltration, TAM repolarization).

Main Results:

• Nanozymes regulate reactive oxygen species, alleviate hypoxia, and deplete antioxidants.
• Nanozymes induce immunogenic cell death, ferroptosis, and cuproptosis.
• Nanozymes promote dendritic cell maturation, enhance cytotoxic T lymphocyte infiltration, and repolarize tumor-associated macrophages to an M1 phenotype, converting "cold" to "hot" tumors.

Conclusions:

• Nanozyme-based catalytic immunoengineering effectively converts "cold" tumors into "hot" tumors by reprogramming the TIME.
• Nanozymes exhibit significant synergistic potential when combined with immune checkpoint blockade, phototherapy, sonodynamic therapy, chemotherapy, and radiotherapy.
• Advanced bioengineered nanozyme platforms hold promise for next-generation combinatorial cancer immunotherapy, pending further research on biosafety and clinical translation.