Biomimetic Metal-Organic Framework Decorated by Artificial Bacterium-Binding Protein and Apamin for Treatment of...

Acute enteritis, commonly categorized into infectious and noninfectious types, shares similar pathological and clinical manifestations through activation of intestinal immune responses and disruption of mucosal functions. In this study, we constructed the virus assembly mimicking zeolitic imidazolate framework-8 (ZIF-8) particles ZIF@Ap+CDGFP against both infectious and noninfectious acute enteritis. The particles were synthesized by loading of the anti-inflammatory peptide apamin (Ap) into ZIF-8, followed by surface decoration of the artificial bacterium-binding protein CDGFP. The protein was designed by fusing the bacterial lipopolysaccharide-binding domain of CD14 and green fluorescence protein and expressed in the engineered Saccharomyces cerevisiae cells. ZIF@Ap+CDGFP significantly reduced lipopolysaccharide-induced apoptosis and reactive oxygen species production in intestinal epithelial cells. In both Salmonella-induced infectious enteritis and dextran sulfate sodium-induced noninfectious enteritis mouse models, ZIF@Ap+CDGFP efficiently attenuated the acute enteritis and intestine mucosal damage by mitigating neutrophil infiltration, suppressing the sustained recruitment of macrophages and dendritic cells, downregulating the expression of the pro-inflammatory cytokines (e.g., IL-6, IL-1β, and TNF-α), and upregulating the expression of the anti-inflammatory cytokine IL-10 and the intestine mucosa-repairing protein Nod2. These findings highlight the synthetic-biology-assisted biomimetic metal-organic framework as a promising therapeutic candidate for treating enteritis and other kinds of intestinal inflammation.