Target specific systemic delivery of TGF-beta siRNA/(PEI-SS)-g-HA complex for the treatment of liver cirrhosis
SCIE
SCOPUS
- Title
- Target specific systemic delivery of TGF-beta siRNA/(PEI-SS)-g-HA complex for the treatment of liver cirrhosis
- Authors
- Park, K; Hong, SW; Hur, W; Lee, MY; Yang, JA; Kim, SW; Yoon, SK; Hahn, SK
- Date Issued
- 2011-07
- Publisher
- ELSEVIER SCI LTD
- Abstract
- A target specific systemic delivery system of siRNA therapeutics was successfully developed using reducible polyethyleneimine grafted hyaluronic acid [(PEI-SS)-g-HA] conjugates. The PEI-SS was synthesized by Michael addition of low molecular weight PEI (MW = 2000) with cystaminebisacrylamide (CBA), and grafted to carboxyl groups of HA via amide bond formation after activation with 1-ethy1-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrate (HOBt). The confocal microscopic and fluorometric analyses confirmed the effective cellular uptake of siRNA/(PEI-SS)-g-HA complex by HA receptor mediated endocytosis. In vitro gene silencing efficiency was ca. 80% in the presence of 10 vol % serum and ca. 50% in the presence of 50 vol% serum in B16F1 melanoma cells and activated hepatic stellate cells (HSCs). Furthermore, target specific systemic delivery of apolipoprotein B (ApoB) siRNA/(PEI-SS)-g-HA complex resulted in a drastically reduced ApoB mRNA level down to ca. 20% in a dose-dependent manner. Finally, TGF-beta siRNA/(PEI-SS)-g-HA complex showed a feasible therapeutic effect on liver cirrhosis with a significantly reduced nodule formation, collagen content, and HSC number. The siRNA/(PEI-SS)-g-HA complex can be exploited for the target specific systemic treatment of various liver diseases. (C) 2011 Elsevier Ltd. All rights reserved.
- Keywords
- Hyaluronic acid; Polyethyleneimine; siRNA; Targeted systemic delivery; Liver cirrhosis; HYALURONIC-ACID; GENE-EXPRESSION; RECEPTOR; FIBROSIS; SIRNA; NANOPARTICLES; ACTIVATION; CONJUGATE; THERAPY; CD44
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17323
- DOI
- 10.1016/J.BIOMATERIALS.2011.03.044
- ISSN
- 0142-9612
- Article Type
- Article
- Citation
- BIOMATERIALS, vol. 32, no. 21, page. 4951 - 4958, 2011-07
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- There are no files associated with this item.
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