학회 | 한국고분자학회 |
학술대회 | 2002년 가을 (10/11 ~ 10/12, 군산대학교) |
권호 | 27권 2호, p.32 |
발표분야 | 의료용 고분자 부문위원회 |
제목 | Artery Wall Binding Peptide-Poly(ethylene glycol)-Grafted-Poly(L-lysine)-Based Gene Delivery to Artery Wall Cells |
초록 | Specific cell-targeting ligands can be conjugated to polymeric gene carriers to enhance target specific gene delivery. Artery wall binding peptide (AWBP; Cys-Gly-Arg-Ala-Leu-Val-Asp- Thr-Leu-Lys-Phe-Val-Thr-Gln-Ala-Glu-Gly-Ala-Lys), a specific cell targeting peptide, was conjugated to poly(ethylene glycol)-grafted-poly(L-lysine)(PEG-g-PLL) to enhance the gene transfer to artery wall cells. AWBP-PEG-g-PLL was synthesized by the reaction between the vinylsulfone group of PEG-g-PLL and the thiol group of cystein in AWBP. 1H-NMR analysis was confirmed the composition of the obtained polymer and indicated that four moles of AWBP were reacted to one mole of VS-PEG-g-PLL. The particle size and the shape of AWBP-PEG-g-PLL/pDNA complexes were measured by dynamic light scattering (DLS) and atomic force microscopy(AFM), respectively. The particles of AWBP-PEG-g-PLL/pDNA complexes were spherical with a size of ∼100 nm. It was found in agarose gel retardation assay that AWBP-PEG-g-PLL was able to condense plasmid DNA and reach complete complexation at and above of a charge ratio 1/1(+/-). Transfection efficiency of AWBP-PEG-g-PLL/pDNA complexes was 150-180 times higher than that of control systems, such as PEG-g-PLL/pDNA and PLL/pDNA, in both bovine aorta endothelial cells and smooth muscle cells. Luciferase activities of AWBP-PEG-g-PLL depended on the amount of a free AWBP in bovine aorta endothelial cells and smooth muscle cells, while those of the control carriers such as PLL and PEG-g-PLL were not affected by free AWBP. These results supported that gene transfer of AWBP-PEG-g-PLL/pDNA complexes to bovine aorta wall cells was mediated by specific artery wall cell receptor-mediated endocytosis. Based on this study, it was concluded that a novel gene delivery carrier was successfully synthesized and displayed an important role in the efficient gene delivery to the arterial wall cells. ACKNOWLEDGMENTS The author wishes to thank L.Yu, S.O Han, C.H. Ahn, S.W. Kim and M.K. Jang for their contribution. We acknowledge financial supports from National Institutes of Health(HL-65477) and Korea Science and Engineering Foundation(2001-1-30800-005-1). REFERENCES 1. Kim, J. S., Maruyama, A., Akaike, T. and Kim, S. W.: J. Control. Release, 47, 51(1997). 2. Han, S. H., Mahato, R. I., Sung, Y. K., and Kim, S. W.: Mol. Ther., 2, 302(2002). 3. Nah, J. W., Han, S. O., Ahn, C. H., and Kim, S. W.: J. Control. Release, 78, 273(2002). |
저자 | 나재운 |
소속 | 순천대 |
키워드 | Artery wall binding peptide; gene carrier; LDL receptor |
VOD | VOD 보기 |