Restoration of dysregulated intestinal barrier and inflammatory regulation through synergistically ameliorating hypoxia and scavenging reactive oxygen species using ceria nanozymes in ulcerative colitis.
{"title":"Restoration of dysregulated intestinal barrier and inflammatory regulation through synergistically ameliorating hypoxia and scavenging reactive oxygen species using ceria nanozymes in ulcerative colitis.","authors":"Ying Zhang, Hengyu Lei, Pengchong Wang, Qinyuan Zhou, Jie Yu, Xue Leng, Ruirui Ma, Danyang Wang, Kai Dong, Jianfeng Xing, Yalin Dong","doi":"10.1186/s40824-023-00412-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O<sub>2</sub> could be a promising strategy for UC treatment.</p><p><strong>Methods: </strong>Ceria nanozymes (PEG-CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of PEG-CNPs in intestinal epithelial cells and RAW 264.7 macrophages and their effects on pro-inflammatory macrophages activation. Subsequently, we investigate the biodistribution, pharmacokinetic properties and long-term toxicity of PEG-CNPs in mice. PEG-CNPs are administered intravenously to mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis to test their colonic tissue targeting and assess their anti-inflammatory activity and mucosal healing properties in UC.</p><p><strong>Results: </strong>PEG-CNPs exhibit multi-enzymatic activity that can scavenge ROS and generate O<sub>2</sub>, promote intestinal epithelial cell healing and inhibit pro-inflammatory macrophage activation, and have good biocompatibility. After intravenous administration of PEG-CNPs to colitis mice, they can enrich at the site of colonic inflammation, and reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by scavenging ROS to generate O<sub>2</sub>, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, PEG-CNPs can effectively scavenge ROS in impaired colon tissues and relieve colonic macrophage hypoxia to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development.</p><p><strong>Conclusion: </strong>This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC.</p>","PeriodicalId":9079,"journal":{"name":"Biomaterials Research","volume":"27 1","pages":"75"},"PeriodicalIF":11.3000,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375752/pdf/","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials Research","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s40824-023-00412-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 1
Abstract
Background: Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O2 could be a promising strategy for UC treatment.
Methods: Ceria nanozymes (PEG-CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of PEG-CNPs in intestinal epithelial cells and RAW 264.7 macrophages and their effects on pro-inflammatory macrophages activation. Subsequently, we investigate the biodistribution, pharmacokinetic properties and long-term toxicity of PEG-CNPs in mice. PEG-CNPs are administered intravenously to mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis to test their colonic tissue targeting and assess their anti-inflammatory activity and mucosal healing properties in UC.
Results: PEG-CNPs exhibit multi-enzymatic activity that can scavenge ROS and generate O2, promote intestinal epithelial cell healing and inhibit pro-inflammatory macrophage activation, and have good biocompatibility. After intravenous administration of PEG-CNPs to colitis mice, they can enrich at the site of colonic inflammation, and reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by scavenging ROS to generate O2, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, PEG-CNPs can effectively scavenge ROS in impaired colon tissues and relieve colonic macrophage hypoxia to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development.
Conclusion: This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC.
期刊介绍：
Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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