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A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota
Li, Chenwen1; Zhao, Yang1; Cheng, Juan1; Guo, Jiawei1; Zhang, Qixiong1; Zhang, Xiangjun2; Ren, Jiong3; Wang, Fengchao3; Huang, Jun4; Hu, Houyuan5; Wang, Ruibing2; Zhang, Jianxiang1
2019-09-01
Source PublicationADVANCED SCIENCE
ISSN2198-3844
Volume6Issue:18
Abstract

The incidence and prevalence of inflammatory bowel disease (IBD) increases steadily worldwide. There is an urgent need for effective and safe IBD therapies. Accelerated resolution of inflammation is a new strategy for the management of inflammatory diseases. For effective and safe IBD treatment, herein a smart nanotherapy (i.e. oxidation-responsive nanoparticles containing a proresolving annexin A1-mimetic peptide Ac2-26, defined as AON) is developed, which can release packaged Ac2-26, in response to highly expressed reactive oxygen species (ROS) at diseased sites. AON effectively protects Ac2-26 from degradation in the enzyme-rich environment of the gastrointestinal tract. By delivering this nanotherapy to the inflamed colons of mice with IBD, site-specific release and accumulation of Ac2-26 in response to high levels of ROS at the inflammatory sites are achieved. Mechanistically, the Ac2-26-containing, oxidation-labile nanotherapy AON effectively decreases the expression of proinflammatory mediators, attenuates trafficking and infiltration of inflammatory cells, promotes efferocytosis of apoptotic neutrophils, and increases phenotypic switching of macrophages. Therapeutically, AON reduces symptoms of inflammation, accelerates intestinal mucosal wound healing, reshapes the gut microbiota composition, and increases short-chain fatty acid production. Additionally, oral delivery of this nanomedicine shows excellent safety profile in a mouse model, conferring the confidence for further development of a targeted precision therapy for IBD and other inflammatory diseases. 

KeywordColitis Targeting Gut Microbiota Nanotherapy Proresolving Peptide Reactive Oxygen Species
DOI10.1002/advs.201900610
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, MultidisciplinarynanoScience & Nanotechnologymaterials Science, Multidisciplinary
WOS IDWOS:000478040200001
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Cited Times [WOS]:80   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Institute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorZhang, Jianxiang
Affiliation1.Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, 400038, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao
3.State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China
4.Institute for Molecular Engineering, University of Chicago, Chicago, 60637, IL, United States
5.Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
Recommended Citation
GB/T 7714
Li, Chenwen,Zhao, Yang,Cheng, Juan,et al. A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota[J]. ADVANCED SCIENCE,2019,6(18).
APA Li, Chenwen,Zhao, Yang,Cheng, Juan,Guo, Jiawei,Zhang, Qixiong,Zhang, Xiangjun,Ren, Jiong,Wang, Fengchao,Huang, Jun,Hu, Houyuan,Wang, Ruibing,&Zhang, Jianxiang.(2019).A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota.ADVANCED SCIENCE,6(18).
MLA Li, Chenwen,et al."A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota".ADVANCED SCIENCE 6.18(2019).
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