Biomimetic Vesicle-Loaded Ce-Mn Bimetallic Nanozyme for Macrophage Reprogramming and Alleviation of Inflammatory Kidney Injury

Abstract

Inflammatory kidney injury, including acute kidney injury, is driven by excessive reactive oxygen species (ROS) and pro-inflammatory M1 macrophage infiltration. Herein, we developed a biomimetic vesicle-loaded cerium-manganese bimetallic nanozyme (CeMn@MV) for targeted macrophage reprogramming. CeMn nanoparticles were synthesized via thermal decomposition and encapsulated within macrophage-derived membrane vesicles. Characterization revealed uniform spherical morphology, stable hydrodynamic size, and efficient cellular uptake. CeMn@MV exhibited broad-spectrum ROS scavenging activities, including DPPH, ABTS, hydroxyl radical, and superoxide anion elimination, as well as catalase-like H?O? decomposition. In HK-2 tubular epithelial cells and RAW264.7 macrophages, CeMn@MV markedly reduced H?O?-induced intracellular ROS. Furthermore, in LPS-stimulated macrophages, CeMn@MV significantly decreased the CD86? M1 population and increased the CD206? M2 population, accompanied by downregulation of TNF-?, IL-1?, and IL-6 and upregulation of IL-10 and TGF-?. These findings demonstrate that CeMn@MV effectively scavenges ROS and reprograms macrophages toward an anti-inflammatory phenotype, providing a promising biomimetic nanozyme strategy for inflammatory kidney injury treatment.