ZnO@Cu5.4O Nanoparticle Alleviates Inflammatory Responses of Intestinal Epithelial Cells by Inhibiting the Expression of GSDMB.

Inflammatory bowel disease is an idiopathic chronic inflammatory condition of the gastrointestinal tract, closely associated with autophagy and pyroptosis. Nanoparticles, as small-diameter particles, play a unique role in disease research. In this study, a one-pot method was used to synthesize ZnO@Cu5.4O nanoparticles and characterize them. To simulate the inflammatory process of intestinal epithelial cells, a coculture system of NK cells and NCM460 cells was established. Proteomics and Western blot experiments were used to measure the expression levels of the relevant proteins. Notably, 0.5ZnO@Cu5.4O demonstrated a strong inhibitory effect on GSDMB, an effect not observed with ZnO or Cu5.4O alone. Proteins in the 0.5ZnO@Cu5.4O group were significantly enriched in the autophagy signaling pathway. 0.5ZnO@Cu5.4O was able to significantly promote the expression of IFN-γ, IL-6, TNF-α, and IL-1β in the NCM460 and NK cell coculture system and also exhibited a remarkable inhibitory effect on inflammatory factors and reactive oxygen species. In vivo experiments revealed that the median lethal dose of 0.5ZnO@Cu5.4O was 52.78 mg/kg. Furthermore, 0.5ZnO@Cu5.4O greatly alleviated the symptoms in a DSS-induced inflammatory bowel disease model. After treatment with 0.5ZnO@Cu5.4O, serum levels of IL-6 and TNF-α in mice were significantly reduced. These findings provide new insights into the therapeutic potential of 0.5ZnO@Cu5.4O for IBD.