Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes....

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Main Authors: Xu, Ting, Ning, Xiaogang, Wu, Jiayan, Wang, Qian, Wang, Zhifei, Chen, Zhiqing, Tang, Xiaoxian, Bai, Peirong, Pu, Kanyi, Li, Liping, Zhang, Ruiping
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/174695
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1746952024-04-12T15:32:09Z Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease Xu, Ting Ning, Xiaogang Wu, Jiayan Wang, Qian Wang, Zhifei Chen, Zhiqing Tang, Xiaoxian Bai, Peirong Pu, Kanyi Li, Liping Zhang, Ruiping School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Inflammatory bowel disease Metabolic regulation Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment. Submitted/Accepted version This work was financially supported by the National Key R&D Program of China, 2023YFC3402800, the National Nature Science Foundation of China (U22A20349, 82120108016, 82071987, and 82001962), the Central Government Guided Local Science and Technology Development Fund Research Project (YDZJSX20231A055), Key Laboratory of Nanoimaging and Drug-loaded Preparation of Shanxi Province (NO: 202104010910010). 2024-04-08T02:03:36Z 2024-04-08T02:03:36Z 2024 Journal Article Xu, T., Ning, X., Wu, J., Wang, Q., Wang, Z., Chen, Z., Tang, X., Bai, P., Pu, K., Li, L. & Zhang, R. (2024). Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease. ACS Nano, 18(9), 7123-7135. https://dx.doi.org/10.1021/acsnano.3c11496 1936-0851 https://hdl.handle.net/10356/174695 10.1021/acsnano.3c11496 38390866 2-s2.0-85186184955 9 18 7123 7135 en ACS Nano © 2024 American Chemical Society. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1021/acsnano.3c11496. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Inflammatory bowel disease
Metabolic regulation
spellingShingle Medicine, Health and Life Sciences
Inflammatory bowel disease
Metabolic regulation
Xu, Ting
Ning, Xiaogang
Wu, Jiayan
Wang, Qian
Wang, Zhifei
Chen, Zhiqing
Tang, Xiaoxian
Bai, Peirong
Pu, Kanyi
Li, Liping
Zhang, Ruiping
Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
description Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment.
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Xu, Ting
Ning, Xiaogang
Wu, Jiayan
Wang, Qian
Wang, Zhifei
Chen, Zhiqing
Tang, Xiaoxian
Bai, Peirong
Pu, Kanyi
Li, Liping
Zhang, Ruiping
format Article
author Xu, Ting
Ning, Xiaogang
Wu, Jiayan
Wang, Qian
Wang, Zhifei
Chen, Zhiqing
Tang, Xiaoxian
Bai, Peirong
Pu, Kanyi
Li, Liping
Zhang, Ruiping
author_sort Xu, Ting
title Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
title_short Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
title_full Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
title_fullStr Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
title_full_unstemmed Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
title_sort metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease
publishDate 2024
url https://hdl.handle.net/10356/174695
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