Immunotherapy strategy for treating inflammatory bowel disease based on a nanozyme/total glucosides of paeony hybrid materials

Abstract

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory condition that has long plagued patients. Herein, an innovative oral treatment strategy for IBD is proposed, which utilizes calcium alginate hydrogel as a carrier to deliver Co₃O₄ nanocages loaded with total glucosides of paeony (TGP) into the body. This design ingeniously exploits the protective properties of the alginate outer layer to ensure that the enzyme is not prematurely degraded when passing through acidic gastric juice. However, upon reaching the inflamed intestinal site, the overexpressed H₂O₂ there mixes with a specific solution, causing the hydrogel to degrade and release Co₃O₄@TGP. These negatively charged nanozymes can precisely recognize and accumulate in the inflamed colonic tissue, achieving targeted therapy through their unique charge characteristics. More importantly, Co₃O₄ itself possesses excellent catalytic activity, effectively consuming excess H₂O₂ at the site of inflammation and degrading into 10 nm small particles in the process, while simultaneously releasing TGP. Together, they exert dual effects of scavenging reactive oxygen species (ROS) and anti-inflammation. Its therapeutic mechanism involves fine regulation of the expression of key proteins such as TLR7, MYD88, and GAPDH, as well as effective inhibition of the NF-κB signaling pathway. This series of actions not only reduces the release of various pro-inflammatory cytokines (such as TNF-α, IL-18, IL-1β, IL-6, and HMGB1) but also promotes the production of the anti-inflammatory cytokine IL-10, thereby effectively maintaining the integrity of the intestinal barrier. This research achievement opens up a novel path for the treatment of colitis.