한빛사논문
- 조회337
Afia Tasnim Rahman 1,2, Jongoh Shin 1, Chang-Hee Whang 1,2, Wonsik Jung 1,2, Dohyun Yoo 1,2, Changjin Seo 1,2, Byung-Kwan Cho 1, Sangyong Jon 1,2
1Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
2Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Republic of Korea.
A.T.R. and J.S. contributed equally to this work.
Corresponding Authors : Byung-Kwan Cho, Sangyong Jon
Abstract
Inflammatory bowel disease (IBD) manifests as intestinal barrier destruction, mucosal immunity dysregulation, and disrupted gut microbiome homeostasis. Conventional anti-inflammatory medications for IBD therapy partially alleviate symptoms but are unable to restore normal barrier and immune function. Here, we report a nanomedicine comprising bilirubin (BR)-attached low-molecular-weight, water-soluble chitosan nanoparticles (LMWC-BRNPs), that promotes restoration of the intestinal barrier, mucosal immunity, and the gut microbiome, thereby exerting robust therapeutic efficacy. In a mouse model of dextran sulfate sodium salt (DSS)-induced colitis, orally administered LMWC-BRNPs were retained in the GI tract much longer than other nonmucoadhesive BRNPs owing to the mucoadhesiveness of LMWC via electrostatic interaction. Treatment with LMWC-BRNPs led to considerable recovery of the damaged intestinal barrier compared with the current IBD medication, 5-aminosalicylic acid (5-ASA). Orally administered LMWC-BRNPs were taken up by pro-inflammatory macrophages and inhibited their activity. They also concurrently increased the population of regulatory T cells, thereby leading to the recovery of dysregulated mucosal immunity. An analysis of the gut microbiome revealed that LMWC-BRNPs treatment significantly attenuated the increase Turicibacter, an inflammation-related microorganism, resulting in protection of gut microbiome homeostasis. Taken together, our findings indicate that LMWC-BRNPs restored normal functions of the intestine and have high potential for use as a nanomedicine for IBD therapy.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-05-30)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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