A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease

J Nanobiotechnology. 2022 Mar 4;20(1):107. doi: 10.1186/s12951-022-01319-7.

Abstract

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.

Keywords: Ceria nanoparticles; Inflammatory bowel disease; Macrophages; Proinflammatory microenvironment; Reactive oxygen species.

MeSH terms

  • Animals
  • Colitis* / drug therapy
  • Colon / metabolism
  • Cytokines / metabolism
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Inflammatory Bowel Diseases* / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oxidative Stress

Substances

  • Cytokines
  • NF-kappa B
  • Dextran Sulfate