An oral nano-antioxidant for targeted treatment of inflammatory bowel disease by regulating macrophage polarization and inhibiting ferroptosis of intestinal cells

Inflammatory bowel disease (IBD) is a chronic inflammatory disease that characterized by excessive reactive oxygen species (ROS) and high ferroptosis. The ROS plays an essential role in macrophage polarization to maintain inflammation and the ferroptosis disrupts intestinal barrier for development of IBD. Herein, an oral nano-antioxidant (Ce-Cur@MCS) was developed by encapsulating nanoceria (CeO2) and curcumin (Cur) to mannose modified chitosan (MCS). Due to the macrophage targeting property, the nano-antioxidant specially deliver to colonic inflammation site, especially to macrophages. It mimics both superoxide dismutase (SOD) and catalase (CAT) to eliminate ROS and scavenge hydroxyl radical in vitro. It can reduce the secretion of inflammatory factors of M1 and deficient M2 macrophage polarization. More important, it can also increase the expression of GSH and GPX4 to protect intestinal cells away from ferroptosis. The results in vivo further confirmed our formed oral nano-antioxidant can enhance therapeutic efficacy of IBD by suppressing macrophage induced inflammation and inhibiting ferroptosis of intestinal cells. In addition, it can increase the abundance and diversity of the gut microflora to maintain therapeutic efficacy of IBD. We envision that scavenging ROS including ferroptosis induced ROS is a viable therapeutic strategy for IBD and our formed oral nano-antioxidant has a promising application for clinical treatment of IBD.