Immunomodulatory Nanozymes as Programmable Redox-Immune Set-Point Regulators

Nanozymes are engineered nanomaterials possessing intrinsic enzyme-mimetic catalytic activities that enable regulation of reactive oxygen species (ROS). Initially developed for superoxide dismutase-, catalase-, and peroxidase-like antioxidant functions, nanozymes are increasingly recognized as modulators of immune responses through redox-dependent mechanisms. Given that ROS participate in immune activation, metabolic regulation, and inflammatory resolution, controlled catalytic modulation offers a strategy for disease-specific immune regulation. This review summarizes recent advances in nanozyme-mediated immunomodulation and discusses how macrophages, neutrophils, dendritic cells, and T lymphocytes respond to redox perturbations. In contrast to prior reviews that classify nanozymes mainly by composition or catalytic type, we propose a redox-immune set-point framework that integrates cell-specific immunometabolism, disease-distorted redox landscapes, and nanozyme design principles. We categorize cerium-, manganese-, iron-based, and metal-free nanozymes according to catalytic properties and therapeutic applications. Across chronic inflammatory disorders, impaired wound healing, tumor microenvironments, and sterile neuroinflammatory or cardiovascular injury, nanozymes demonstrate distinct immune regulatory patterns, including resolution restoration, regenerative coordination, antitumor immune reactivation, and attenuation of inflammasome-associated damage. Finally, we address translational challenges such as spatiotemporal control, cell-specific targeting, biodegradability, and biosafety, emphasizing the importance of precision redox engineering for future clinical development.