The escalating global threat of multidrug-resistant (MDR) bacterial infections necessitates the development of alternative therapeutic strategies beyond traditional antibiotics. In this study, we synthesized gold-copper alloy (AuCu₃) nanozymes to address this challenge and investigated their catalytic efficiency, mechanisms, and interactions with the host immune system. We employed in vitro assays against carbapenem-resistant Klebsiella pneumoniae (CRKP), murine infection models, and clinical cases of otitis externa to evaluate therapeutic efficacy. Furthermore, single-cell RNA sequencing was utilized to elucidate the underlying immunomodulatory pathways. Our results demonstrate that AuCu3 nanozymes exhibit potent peroxidase-like activity, catalyzing the conversion of hydrogen peroxide (H₂O₂) into cytotoxic hydroxyl radicals. This reaction achieves broad-spectrum, irreversible bacterial elimination within three hours through synergistic membrane disruption and DNA degradation. In both animal models and clinical applications, the AuCu₃/H₂O₂ system effectively eradicated MDR infections and accelerated tissue repair without inducing systemic toxicity. Mechanistically, transcriptomic analysis revealed that AuCu₃ triggers immunometabolic reprogramming in monocytes, shifting their metabolism from glycolysis to oxidative phosphorylation. This metabolic transition enhances innate immune recruitment, while concurrent activation of copper homeostatic pathways ensures cellular equilibrium. Consequently, AuCu₃ represents a promising dual-action therapeutic platform that combines direct antimicrobial activity with host-directed immune modulation to combat intractable infections and promote wound healing.

Multiphase catalysis is used in many industrial processes; however, the reaction rate can be restricted by the low accessibility of gaseous reactants to the catalysts in water, especially for oxygen-dependent biocatalytic reactions. Despite the fact that solubility and diffusion rates of oxygen in many liquids (such as perfluorocarbon) are much higher than in water, multiphase reactions with a second liquid phase are still difficult to conduct, because the interaction efficiency between immiscible phases is extremely low. Herein, we report an efficient triphase biocatalytic system using oil core-silica shell oxygen nanocarriers. Such design offers the biocatalytic system an extremely large water-solid-oil triphase interfacial area and a short path required for oxygen diffusion. Moreover, the silica shell stabilizes the oil nanodroplets in water and prevents their aggregation. Using oxygen-dependent oxidase enzymatic reaction as an example, we demonstrate this efficient biocatalytic system for the oxidation of glucose, choline, lactate, and sucrose by substituting their corresponding oxidase counterparts. A rate enhancement by a factor of 10-30 is observed when the oxygen nanocarriers are introduced into reaction system. This strategy offers the opportunity to enhance the efficiency of other gaseous reactants involved in multiphase catalytic reactions.

The wetting properties of an electrode surface are of significant importance to the performance of electrochemical devices because electron transfer occurs at the electrode/electrolyte interface. Described in this paper is a low-cost metal oxide electrocatalyst (CuO)-based high-performance sensing device using an enzyme electrode with a solid/liquid/air triphase interface in which the oxygen level is constant and sufficiently high. We apply the sensing device to detect glucose, a model test analyte, and demonstrate a linear dynamic range up to 50 mM, which is about 25 times higher than that obtained using a traditional enzyme electrode with a solid/liquid diphase interface. Moreover, we show that sensing devices based on a triphase assaying interface are insensitive to the significant oxygen level fluctuation in the analyte solution.