Multifunctional two-dimensional Bi₂Se₃ nanodiscs for anti-inflammatory therapy of inflammatory bowel diseases

The overexpression of reactive oxygen and nitrogen species (RONS) in the colonic mucosa destroys the mucosa and its barrier, accelerating the occurrence of inflammatory bowel disease (IBD). The elimination of RONS from the inflammatory colon has proven effective in alleviating IBD. Although many nanoantioxidants have been developed, preparing robust and efficient nano-antioxidants remains challenging. Herein, by modifying bismuth selenide (Bi₂Se₃) nanodiscs with polyvinylpyrrolidone (PVP), a multifunctional nanozyme based on 2D nanomaterials was developed for the treatment of IBD. By eliminating multiple RONS, such as hydroxyl radicals (•OH), superoxide anions (O₂^-•), nitric oxide (NO), and Bi₂Se₃ nanodiscs enhanced cellular survival after H₂O₂ stimulation. As evidenced by colonic injury, reduced body weight, spleen index, and proinflammatory cytokine levels in mice, RONS clearance alleviated intestinal inflammation in a prevention and delay model of acute colitis. 16S rDNA amplicon sequencing reveals that Bi₂Se₃ nanodiscs had the potential to regulate intestinal flora, increase the proportion of Firmicutes to Bacteroidetes, inhibit Proteobacteria bacteria, and restore intestinal homeostasis. This study highlights the use of Bi₂Se₃ nanodiscs with excellent biocompatibility, multienzyme functionality, and RONS scavenging ability as treatments for IBD without apparent adverse effects. STATEMENT OF SIGNIFICANCE: RONS were efficiently scavenged by Bi₂Se₃ nanodiscs. Bi₂Se₃ nanodiscs could be as a promising and potentially safe theraeputic agent for IBD. The gut microbiota could be modulated by Bi₂Se₃ nanodiscs.