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....
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/174695 |
| _version_ | 1826122787030302720 |
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| author | Xu, Ting Ning, Xiaogang Wu, Jiayan Wang, Qian Wang, Zhifei Chen, Zhiqing Tang, Xiaoxian Bai, Peirong Pu, Kanyi Li, Liping Zhang, Ruiping |
| 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 |
| author_sort | Xu, Ting |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T05:53:55Z |
| format | Journal Article |
| id | ntu-10356/174695 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:53:55Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-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 |
| 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 |
| title | 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_short | Metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease |
| title_sort | metabolic nanoregulator remodels gut microenvironment for treatment of inflammatory bowel disease |
| topic | Medicine, Health and Life Sciences Inflammatory bowel disease Metabolic regulation |
| url | https://hdl.handle.net/10356/174695 |
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