Resveratrol-embedded hollow cerium oxide nanomedicine targeted treat inflammatory bowel disease through ROS clearance, intestinal mucosal immune homeostasis recovery and gut microbiota modulation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is difficult to cure. The crucial pathogenic factors of IBD are mainly caused by the overexpression of pro-inflammatory cytokines and the disturbance of gut microbiota triggered by excessive reactive oxygen species (ROS). Herein, the resveratrol-embedded hollow cerium oxide composite nanomaterials with surface modified hyaluronic acid (Res-CeO 2 @HA) is developed to restore intestinal mucosal immune homeostasis and modulate gut microbiota via effective elimination of ROS-inflammation. The synthetic nanomedicine integrates the enzyme-like activity of CeO 2 , the antioxidant properties of Res, and the targeting capabilities of HA. Results showed that Res-CeO 2 @HA had significant advantages in ROS clearance and colon targeting. And it balanced the expression of inflammatory cytokines by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and modulating the TLR4/NF-κB signaling pathway to alleviate IBD in mice. Furthermore, it is found that Res-CeO 2 @HA significantly improved the homeostasis of the intestinal microbiota. This friendly and multifunctional nanomedicine may provide new strategies for the clinical treatment of IBD.