Journal
BIOACTIVE MATERIALS
Volume 18, Issue -, Pages 433-445Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2022.03.031
Keywords
Nanomicelle; Injectable hydrogel; Peptide display; Theranostic; All-in-one treatment; Inflammatory bowel disease
Funding
- Bio & Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIT) [2019R1A2C2010802]
- Korea Medical Device Development Fund Grant - Ministry of Science and ICT
- Ministry of Health Welfare
- Ministry of Food and Drug Safety [1711138302, KMDF_PR_20200901_0152]
- Starting Growth Technological R&D program of SMBA [S2798389]
- National Cancer Institute of the National Institutes of Health [R21CA236690]
- Ministry of Trade, Industry and Energy
- Korea Technology & Information Promotion Agency for SMEs (TIPA) [S2798389] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2019R1A2C2010802] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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All-in-one treatments represent a paradigm shift in future medicine, allowing the treatment of inflammatory bowel disease (IBD) through endoscopic spray of injectable hydrogels. Peptide conjugation to the hydrogels enables guided monitoring of intestinal lesions and drug-free therapy by suppressing inflammatory signaling.
All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.
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