Nanozyme-Mediated Anesthetic Drug Delivery and Macrophage Immunomodulation: Emerging Concepts and Translational Challenges.

Anesthetic agents can influence not only neuronal signaling but also oxidative stress, inflammasome activation, cellular metabolism, and perioperative immune responses. Macrophages are central regulators of tissue injury, inflammation resolution, neuroimmune interactions, and the tumor microenvironment, and therefore represent a plausible target for non-neuronal effects of anesthetic therapy. Nanozymes are nanomaterials with intrinsic enzyme-like catalytic activity; representative systems include cerium oxide and magnetite/iron-oxide nanoparticles with superoxide dismutase-, catalase-, peroxidase-, or related redox activities. Unlike conventional inert nanocarriers, nanozymes may combine drug loading with active remodeling of reactive oxygen species, hypoxia, and inflammatory microenvironments. However, direct studies that simultaneously demonstrate nanozyme-mediated anesthetic delivery, macrophage-dependent mechanisms, and therapeutic benefit remain scarce. Current evidence is therefore derived mainly from three adjacent areas: nanozyme regulation of macrophages, anesthetic modulation of macrophage function, and nanocarrier-mediated delivery of anesthetic agents. This review critically integrates these evidence streams, discusses redox regulation, inflammasome signaling, metabolic reprogramming, biological clearance, and context-dependent pro-oxidative versus antioxidant activity, and evaluates strategies for targeted and stimulus-responsive anesthetic delivery. We further compare nanozyme platforms with other advanced nanocarriers and highlight key translational barriers, including assay standardization, macrophage heterogeneity, long-term inorganic-material retention, and clinically meaningful pharmacodynamic evaluation. These emerging concepts provide a framework for testable perioperative drug-delivery and immunomodulation strategies rather than evidence of an already established clinical platform.