Hyaluronic acid–tumor necrosis factor-related apoptosis-inducing ligand conjugate for targeted treatment of liver fibrosis
SCIE
SCOPUS
- Title
- Hyaluronic acid–tumor necrosis factor-related apoptosis-inducing ligand conjugate for targeted treatment of liver fibrosis
- Authors
- Yang, JA; Kong, WH; Sung, DK; Kim, H; Kim, TH; Lee, KC; Hahn, SK
- Date Issued
- 2015-01-15
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Abstract
- Liver fibrosis is a chronic liver disease caused by viral infection and/or metabolic, genetic and cholestatic disorders. The inhibition of hepatic stellate cell (HSC) activation and the selective apoptosis of activated HSCs can be a good strategy to treat liver fibrosis. The activated HSCs are known to be more susceptible to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis than normal HSCs because death receptor 5 is overexpressed on the cell surface. In this work, a target-specific and long-acting hyaluronic acid (HA)-TRAIL conjugate was successfully developed for the treatment of liver fibrosis. The HA-TRAIL conjugate was synthesized by a coupling reaction between aldehyde-modified HA and the N-terminal amine group of TRAIL. The biological activity of the HA-TRAIL conjugate was confirmed by an in vitro anti-proliferation assay and caspase-3 expression in human colon cancer HCT116 cells. In vivo real-time bioimaging exhibited the target-specific delivery of near-infrared fluorescence dye-labeled HA-TRAIL conjugate to the liver in mice. According to pharmacokinetic analysis, the HA-TRAIL conjugate was detected for more than 4 days after single intravenous injection into Sprague-Dawley (SD) rats. Finally, we could confirm the antifibrotic effect of HA-TRAIL conjugate in an N-nitrosodimethylamine-induced liver fibrosis model SD rats. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27154
- DOI
- 10.1016/J.ACTBIO.2014.10.002
- ISSN
- 1742-7061
- Article Type
- Article
- Citation
- ACTA BIOMATERIALIA, vol. 12, page. 174 - 182, 2015-01-15
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.