Cu–Zn@HA bimetallic nanozymes: a novel approach for ROS clearance and macrophage polarization in colitis therapy

Inflammatory bowel disease (IBD) presents significant clinical challenges due to its multifaceted pathogenesis and the limited efficacy of existing therapies. This study investigates the therapeutic potential of Cu–Zn@HA bimetallic nanozymes for the treatment of colitis. Through in vivo experiments, we demonstrated that these nanozymes exhibit sustained retention in the colon, facilitating effective modulation of gut microbiota composition and diversity. Notably, Cu–Zn@HA nanozymes significantly enhanced α-diversity and induced distinct alterations in microbial community structure across treatment groups. While no marked differences were observed in the Firmicutes/Bacteroidetes ratio, our biomarker analyses indicated critical shifts in bacterial populations associated with gut health and inflammatory responses. Additionally, Cu–Zn@HA nanozymes effectively scavenged reactive oxygen species (ROS) and promoted macrophage polarization, contributing to an anti-inflammatory microenvironment. Importantly, our studies confirmed the excellent safety profile of these nanozymes. Collectively, these findings underscore the promising role of Cu–Zn@HA bimetallic nanozymes as a novel therapeutic strategy for IBD, paving the way for future investigations into their clinical efficacy and safety.