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

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.

Recent Advancements in the Formulation of Nanomaterials-Based Nanozymes, Their Catalytic Activity, and Biomedical Applications

“…144 Furthermore, a dextran-coated cerium oxide (D-CeO 2 ) nanozyme with superoxide dismutase and catalase activities was demonstrated to exhibit ROS scavenging activity and suppress pro-inflammatory cytokines to protect cells from H 2 O 2 -induced oxidative stress. 145 In addition to this, a Cu-only superoxide dismutase (SOD5)-based single atom nanozyme (Cu-SAzyme) dramatically decreased various organ damage and death in activated inflammatory cells by eliminating excess ROS and pro-inflammatory cytokines. 146 Therefore, it can be concluded that nanozymes can serve as potential ROS scavengers and cytokine modulators to induce the antiinflammatory response.…”

“…Moreover, the Prussian blue (PB) nanozyme was investigated as a novel compound for repairing cutaneous wounds via the reduction of excessive ROS and inflammatory regulation . Furthermore, a dextran-coated cerium oxide (D-CeO 2 ) nanozyme with superoxide dismutase and catalase activities was demonstrated to exhibit ROS scavenging activity and suppress pro-inflammatory cytokines to protect cells from H 2 O 2 -induced oxidative stress . In addition to this, a Cu-only superoxide dismutase (SOD5)-based single atom nanozyme (Cu-SAzyme) dramatically decreased various organ damage and death in activated inflammatory cells by eliminating excess ROS and pro-inflammatory cytokines .…”

Prospective therapeutics for intestinal and hepatic fibrosis

“…Cao et al developed a dextran‐coated cerium oxide (D‐CeO 2 ) nanozyme by chemical precipitation which has potent ROS scavenging abilities to alleviate intestinal fibrosis. The D‐CeO 2 nanozyme efficiently scavenged ROS and regulated the fibrosis‐related microenvironment in TNBS‐ and DSS‐induced intestinal fibrosis mice models, providing a practical use for nanozymes with ROS scavenging capabilities in anti‐fibrotic strategies 63 …”

“…Evidence indicates that ROS activates and promotes TGF-β signaling, in turn, TGF-β1 boosts ROS production and decreases its elimination, which promotes fibrogenesis. 62 63…”

Dual‐Targeted Nanoparticle‐in‐Microparticle System for Ulcerative Colitis Therapy

“…Hence, ALG is a promising material for colon targeting. [17,18] Therefore, we hypothesized that ALG-coated Man-biotin dual-modified polymer microspheres might be an intelligent oral targeted delivery system for UC. Scheme 1.…”