Single-Atom Nanozymes for High-Efficiency Cancer Immunotherapy by Targeting Tumor Microenvironment

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Immunology

Background:

• Tumor immunotherapy faces challenges due to the immunosuppressive tumor microenvironment (TME).
• The TME hinders immune cell infiltration, effector cell activity, and promotes immune escape.
• Single-atom nanozymes (SAzymes) are emerging as a promising nanomedicine platform to address these limitations.

Purpose of the Study:

• To review the mechanisms by which SAzymes remodel the TME and enhance cancer immunotherapy.
• To discuss recent advances in SAzyme design and multimodal synergistic therapy.
• To highlight challenges and future perspectives for SAzyme-based cancer immunotherapy.

Main Methods:

• SAzymes leverage their atomic precision and tunable electronic structures for enzyme-like catalytic activities.
• Catalytic therapy by SAzymes targets TME components like hypoxia and lactate.
• SAzymes reprogram immunosuppressive cells and induce immunogenic cell death (ICD).

Main Results:

• SAzymes effectively alleviate hypoxia, regulate lactate accumulation, and disrupt redox homeostasis within the TME.
• SAzyme-mediated therapy induces ICD, significantly enhancing antitumor immune responses.
• Quantitative structure-activity relationships (QSAR) enable rational design and optimization of SAzymes.

Conclusions:

• SAzymes represent a powerful strategy for overcoming TME-mediated resistance in cancer immunotherapy.
• Atomic-level design and multimodal synergistic approaches are key to maximizing SAzyme efficacy.
• Future directions include machine learning-guided design, biosafety, and clinical translation of SAzymes.