Background Inflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet. Results In this study, dextran-coated cerium oxide (D-CeO2) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H2O2-induced oxidative damage. Moreover, D-CeO2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging. Conclusion We introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that features colonic epithelial barrier dysfunction and gut dysbiosis. Preclinical studies demonstrated that inhibiting the overexpression of CD98 via small...

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects. Materials and Methods: Herein, the hyaluronic acid (HA)-modified L-arginine CO 2 nanoparticles (HA-L-Arg-CO 2 @NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO 2 and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS. Results: HA-L-Arg-CO 2 @NPs show great biocompatibility and the excellent ability to target the colon. Using lipopolysaccharideinduced inflammation in vitro, the prominent anti-inflammatory effect of HA-L-Arg-CO 2 @NPs and HA-PS@NPs is observed. Further, orally administered HA-L-Arg-CO 2 @NPs and HA-PS@NPs via the colon-targeted chitosan/alginate (CA) hydrogel downregulate proinflammatory cytokines and reduce intestinal permeability, yielding significant outcomes in alleviating the symptoms of UC. Conclusion: This pH-activated "nano-bomb" carrier with therapeutic effect can be exploited as efficient oral drug carriers for UC treatment.