Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis
SCIE
SCOPUS
- Title
- Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis
- Authors
- Kim, WJ; Yockman, JW; Lee, M; Jeong, JH; Kim, YH; Kim, SW
- Date Issued
- 2005-08
- Publisher
- ELSEVIER SCIENCE BV
- Abstract
- Vascular endothelial growth factor (VEGF), a potent angiogenic molecule specific for vascular endothelial cells, is overexpressed in most tumors and closely associated with tumor growth and metastasis. It has been shown that a soluble fragment of VEGF receptor Flt-1 (sFIt-1) has anti-angiogenic properties by way of its antagonist activity against VEGF. In the present study, we demonstrated that the stable expression of sFIt-1 by endothelial cell targeted non-viral gene delivery inhibited the angiogenesis of endothelial cells. A targeted polymeric gene delivery system, PEI-g-PEG-RGD, was developed by incorporating the alpha v beta 3/alpha v beta 5 integrin-binding RGD peptide, ACDCRGDCFC (single-letter amino acid code), into the cationic polymer, polyethylenimine (PEI) via a hydrophilic polyethylene glycol (PEG) spacer. The functional analysis of therapeutic gene encoding sFIt-1/carrier complex was performed with an endothelial cell proliferation assay. The complex of sFlt-1 gene with PEI-g-PEG-RGD conjugate efficiently inhibited the proliferation of cultured endothelial cells, representing that expressed sFIt-1 predominantly bound to exogenous VEGF and blocked the binding of VEGF to the full-length Flt-1 receptor. These findings suggest that the combination of targeted gene carrier and sFlt-1 possesses the potential to be an efficient tool for the anti-angiogenic gene therapy to treat cancer. (c) 2005 Elsevier B.V. All rights reserved.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28910
- DOI
- 10.1016/j.jconrel.2005.04.016
- ISSN
- 0168-3659
- Article Type
- Article
- Citation
- JOURNAL OF CONTROLLED RELEASE, vol. 106, no. 1-2, page. 224 - 234, 2005-08
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