A cerium nanocluster for effective alleviation of inflammatory bowel disease by scavenging RONS and regulating gut microbiome

Inflammatory bowel disease (IBD) is characterized by excessive generation of reactive oxygen species and reactive nitrogen species (RONS) within the pro-inflammatory microenvironment. Conventional treatments often have serious side effects, making IBD management challenging. Here, a new cerium cluster, Ce12, with a formula of [Ce₁₂(<i>μ</i> ₃-O)₈(<i>μ</i> ₃-OH)₈(<i>μ</i> ₂-OH)₆(ADA)₁₈]∙3H₂O∙3CH₃CN (ADA^- = 1-adamantanecarboxylate) was prepared and capped with β-cyclodextrin (β-CD) through self-assembly process involving the adamantane moiety of Ce12 and β-CD, resulting in Ce12@CD nanoparticles (NPs). Ce12@CD NPs, with good stability and biocompatibility, exhibit excellent reactive RONS scavenging activities due to the presence of a fraction of Ce³⁺ ions, offering potential for treating inflammatory diseases. Treatment significantly alleviated body weight loss, colon length reduction, and pathological injury of colon in mice with dextran sodium sulfate (DSS)-elicited colitis, thereby repairing the intestinal mucosal barrier and reducing inflammation. RNA sequence analysis revealed that the therapeutic effects of Ce12@CD NPs are highly correlated with IL-17 and TNF signaling pathways, thereby reducing inflammatory factors such as IL-1β and TNF-α, and alleviating intestinal inflammation. Additionally, Ce12@CD NPs successfully modulated DSS-induced gut microbiota imbalances. This work highlights the unique catalytic activity of Ce12@CD NPs in removing RONS and mimicking biological enzymes, showcasing their potential therapeutic applications for inflammatory disorders.