| 초록 |
Polymeric biomaterials have great potential in gene therapy, since the polymers are used not only as a direct vehicle for genes, but also they can be modified chemically to meet requirements. Compared to viral systems, non-viral gene delivery, involving the use of cationic polymer based carriers, have several advantages including nonimmunogenicity, low acute toxicity and flexibility of design. Vascular endothelial growth factor (VEGF) 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 (sFlt-1) has anti-angiogenic properties by way of its antagonist activity against VEGF. To deliver therapeutic genes into specific target sites with high efficacy, we synthesized several polymeric gene delivery vehicles. For targeting angiogenic endothelial cells which induce tumor growth, a PEI-g-PEG-RGD conjugate was developed by incorporating the ανβ3/ανβ5 integrin-binding RGD peptide, to the cationic polymer, PEI via a hydrophilic PEG spacer as a delivery vehicle, and a therapeutic gene, pCMV-sFlt-1 was constructed. The complex of PEI-g-PEG-RGD/pCMV-sFlt-1 showed high transfection efficacy in angiogenic endothelial cells and moreover, intravenous injection of complexes inhibited tumor growth in tumor-bearing mice. |
