Orally administration of cerium oxide nanozyme for computed tomography imaging and anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease

J Nanobiotechnology. 2023 Jan 19;21(1):21. doi: 10.1186/s12951-023-01770-0.

Abstract

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.

Keywords: CT imaging; Cerium oxide nanozyme; Inflammation; Inflammatory bowel disease; Intestinal fibrosis.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Cerium* / pharmacology
  • Cytokines / metabolism
  • Fibrosis
  • Humans
  • Hydrogen Peroxide
  • Inflammation
  • Inflammatory Bowel Diseases* / diagnostic imaging
  • Inflammatory Bowel Diseases* / drug therapy
  • Reactive Oxygen Species / metabolism
  • Tomography
  • Tomography, X-Ray Computed

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • ceric oxide
  • Cerium
  • Cytokines
  • Hydrogen Peroxide
  • Reactive Oxygen Species