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

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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-CeO ₂) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO ₂ 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 H ₂O ₂-induced oxidative damage. Moreover, D-CeO ₂ 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-CeO ₂ 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-CeO ₂ reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO ₂ 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-CeO ₂ 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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12951-023-01770-0.

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Most cited references 62

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TGF-β signaling in fibrosis.

Anna Biernacka, Marcin Dobaczewski, Nikolaos G Frangogiannis (2011)

Transforming growth factor β (TGF-β) is a central mediator of fibrogenesis. TGF-β is upregulated and activated in fibrotic diseases and modulates fibroblast phenotype and function, inducing myofibroblast transdifferentiation while promoting matrix preservation. Studies in a wide range of experimental models have demonstrated the involvement of the canonical activin receptor-like kinase 5/Smad3 pathway in fibrosis. Smad-independent pathways may regulate Smad activation and, under certain conditions, may directly transduce fibrogenic signals. The profibrotic actions of TGF-β are mediated, at least in part, through induction of its downstream effector, connective tissue growth factor. In light of its essential role in the pathogenesis of fibrosis, TGF-β has emerged as an attractive therapeutic target. However, the pleiotropic and multifunctional effects of TGF-β and its role in tissue homeostasis, immunity and cell proliferation raise concerns regarding potential side effects that may be caused by TGF-β blockade. This minireview summarizes the role of TGF-β signaling pathways in the fibrotic response.

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Chemically induced mouse models of acute and chronic intestinal inflammation

Stefan Wirtz, Vanessa Popp, Markus Kindermann … (2017)

This protocol update describes how to generate mouse models of inflammatory bowel diseases and methods for analyzing disease progression.

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Environmental triggers in IBD: a review of progress and evidence

Ashwin Ananthakrishnan, Charles Bernstein, Dimitrios Iliopoulos … (2017)

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

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Author and article information

Contributors

Yuanyuan Zhang: 4120115013@stu.xjtu.edu.cn

Kangsheng Tu: tks0912@foxmail.com

Jie Liang: liangjie@fmmu.edu.cn

Mingzhen Zhang: mzhang21@xjtu.edu.cn

Journal

Journal ID (nlm-ta): J Nanobiotechnology

Journal ID (iso-abbrev): J Nanobiotechnology

Title: Journal of Nanobiotechnology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-3155

Publication date (Electronic): 19 January 2023

Publication date PMC-release: 19 January 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 21

Affiliations

[1 ]GRID grid.452438.c, ISNI 0000 0004 1760 8119, Department of Hepatobiliary Surgery, , The First Affiliated Hospital of Xian Jiaotong University, ; Xi’an, 710061 Shaanxi China

[2 ]GRID grid.43169.39, ISNI 0000 0001 0599 1243, School of Basic Medical Sciences, Xian Key Laboratory of Immune Related Diseases, , Xian Jiaotong University, ; Xi’an, 710061 Shaanxi China

[3 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, , Huazhong University of Science and Technology, ; Wuhan, 430074 Hubei China

[4 ]GRID grid.452438.c, ISNI 0000 0004 1760 8119, Department of Emergency and Critical Care Medicine, , The First Affiliated Hospital of Xi’an Jiaotong University, ; Xi’an, 710061 China

[5 ]GRID grid.43169.39, ISNI 0000 0001 0599 1243, Key Laboratory of Environment and Genes Related to Diseases, , Xian Jiaotong University, Ministry of Education, ; Xi’an, 710061 Shaanxi China

[6 ]GRID grid.417295.c, ISNI 0000 0004 1799 374X, Xijing Hospital of Digestive Diseases, , Air Force Military Medical University, ; Xi’an, 710068 Shaanxi China

Article

Publisher ID: 1770

DOI: 10.1186/s12951-023-01770-0

PMC ID: 9854161

PubMed ID: 36658555

SO-VID: 92a87265-c137-416a-8371-9794cc4e5f6b

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 28 November 2022

Date accepted : 5 January 2023

Funding

Funded by: the National Natural Science Foundation of China

Award ID: 82000523

Award Recipient : Jie Liang

Custom metadata

ScienceOpen disciplines: Biotechnology

Keywords: inflammatory bowel disease,cerium oxide nanozyme,ct imaging,inflammation,intestinal fibrosis

Data availability:

ScienceOpen disciplines: Biotechnology

Keywords: inflammatory bowel disease, cerium oxide nanozyme, ct imaging, inflammation, intestinal fibrosis

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

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Abstract

Background

Results

Conclusion

Supplementary Information

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Karger: Gastroenterology

Most cited references 62

TGF-β signaling in fibrosis.

Chemically induced mouse models of acute and chronic intestinal inflammation

Environmental triggers in IBD: a review of progress and evidence

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