Target Specific Tumor Treatment by VEGF siRNA Complexed with Reducible Polyethyleneimine-Hyaluronic Acid Conjugate
SCIE
SCOPUS
- Title
- Target Specific Tumor Treatment by VEGF siRNA Complexed with Reducible Polyethyleneimine-Hyaluronic Acid Conjugate
- Authors
- Park, K; Lee, MY; Kim, KS; Hahn, SK
- Date Issued
- 2010-07
- Publisher
- ELSEVIER SCIENCE BV
- Abstract
- Target specific delivery of small interfering RNA (siRNA) has been regarded as one of the most important technologies for the development of siRNA therapeutics. In this work, non-toxic low molecular weight (MW) polyethyleneimine (PEI, 2000 Da) was cross-linked with cystamine bisacrylamide (CBA) to prepare reducible PEI-SS in the body. Then, PEI-SS was conjugated with hyaluronic acid (HA) in the form of block-copolymer to enhance serum stability and facilitate target specific cellular uptake of siRNA by HA receptor mediated endocytosis. The cytotoxicity of (PEI-SS)-b-HA conjugate appeared to be negligible likely due to the degradation of PEI-SS to low MW PEI in the cytosol. Flow cytometric and confocal microscopic analyses confirmed the HA receptor mediated endocytosis of siRNA/(PEI-SS)-b-HA complex. The siRNA/(PEI-SS)-b-HA complex demonstrated an excellent in vitro gene silencing efficiency in the range of 50-80% reducing the mRNA expression level in the absence and presence of 50 vol% serum. Moreover, intra-tumoral injection of vascular endothelial growth factor (VEGF) siRNA/(PEI-SS)-b-HA complex resulted in dramatically inhibited tumor growth with reduced VEGF mRNA and VEGF levels in the tumors. (C) 2010 Elsevier Ltd. All rights reserved.
- Keywords
- Hyaluronic acid; Polyethyleneimine; siRNA; Target delivery; Gene silencing; LOW-MOLECULAR-WEIGHT; ENDOTHELIAL GROWTH-FACTOR; MEDIATED GENE DELIVERY; SMALL INTERFERING RNA; INTRACELLULAR DELIVERY; HIV-1 INFECTION; DNA DELIVERY; IN-VIVO; RECEPTOR; THERAPEUTICS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25879
- DOI
- 10.1016/J.BIOMATERIALS.2010.03.018
- ISSN
- 0142-9612
- Article Type
- Article
- Citation
- BIOMATERIALS, vol. 31, no. 19, page. 5258 - 5265, 2010-07
- 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.