Page 8 - ebook

[D. Medicine/Translational Research] D-4

Development of a specific therapeutic agent for intestinal

lesions using injectable nanomicelle hydrogels and

inflammatory bowel disease patient cell chips

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Songhyun Lee¹ , Hyo-Jin Yoon¹ , Tae Young Kim¹ , Suji Park¹, Yong Cheol Shin², Eun Kyung Wang³, Jihye
Noh⁴, Hyun Jung Kim¹,², Cheol Ryong Ku³, Hong Koh⁴, Chang-Soo Kim¹, Young Min Shin¹*, Joon-Sang
Park⁵*, Hak-Joon Sung¹*

¹Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Korea, ²Department of
Biomedical Engineering, The University of Texas at Austin, Texas 78712, USA, ³Department of Internal Medicine,

Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul 03722, Korea,

⁴Department of Pediatrics, Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea, ⁵
Department of Computer Engineering, Hongik University, Seoul 04066, Korea

Inflammatory bowel disease (IBD) is an unknown disease that causes chronic inflammation of the gastrointestinal

tract due to abnormal activation of the immune system. The causes of IBD are considered to be genetic
predisposition, environmental factors, immune response, intestinal microorganism, but have not yet been clearly
identified. When the composition of intestinal microorganism is changed by IBD, immune cells are activated and

the secretion of cytokines that cause inflammation is promoted. For the treatment, many studies are being

conducted to suppress or inhibit the secretion of cytokines that cause inflammation. In this study, a peptide designed
as an antagonist of a major component mediating intestinal infection by Bacillus subtilits flagellin during initiation
of IBD was prepared and conjugated to an injectable nanomicelle hydrogel. The peptide-guided nanomicelle

hydrogel is efficiently attached onto Toll-like receptor 5 (TLR5) as a main target of the flagellin binding as well as

Notch-1. Antagonistic binding of the peptides without any drug potently inhibited inflammatory signaling in which
TLR5 and Notch-1 act cooperatively through the downstream action of tumor necrosis factor (TNF-a). Results were
verified using human colorectal cell lines (Caco-2), clinical IBD patient cells, IBD mimic chip, mouse IBD model, and

pig experiments.