Gene delivery system using polyelectrolyte complex micelles = 나노 미셀 구조를 이용한 유전자 전달 시스템

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A polyelectrolyte complex micelle (PECM)-based delivery system of antisense oligonucleotide (ODN) was demonstrated for targeting tumors. The tumor targeting property was conferred to the PECM by incorporating folate (FOL) to the end of polyelthyleneglycol (PEG) segment in ODN-PEG conjugate (ODN-PEG-FOL). When treated in FOL receptor over-expressing cells, the PECMs of the ODN-PEG-FOL conjugate showed a significant reduction in green fluorescent protein (GFP) expression in dose dependant manner. The enhanced transfection of ODN-PEG-FOL PECMs showed dependency on the presence of a folate receptor in target cells. The presence of free folate in the transfection medium significantly affects the cellular association of ODN-PEG-FOL PECMs. The efficacy of target specific gene suppression by ODN-PEG-FOL PECMs was maintained under the serum containing transfection medium. The results suggest that the PECM-based gene delivery system could be a promising candidate for a cancer targeted gene therapy. A target-specific delivery system of anti-GFP small interfering RNA (siRNA) plasmid was developed by using FOL-modified cationic polyethylenimine (PEI). A GFP siRNA plasmid (pSUPER-siGFP), inhibiting the synthesis of GFP, was constructed and used for inhibiting GFP expression in FOL receptor over-expressing cells (KB cells) in a target specific manner. PEI-PEG-FOL conjugate was synthesized as a pSUPER-siGFP plasmid vector. KB cells expressing GFP were treated with various formulations of pSUPER-siGFP/PEI-PEG-FOL complexes to inhibit the gene expression of GFP. The formulated complexes were characterized under various conditions and their GFP gene inhibition and cellular uptake behaviors were explored by confocal microscopy and flow cytometry analysis. The pSUPER-siGFP/PEI-PEG-FOL complexes inhibited the GFP expression of KB cells more effectively than pSUPER-siGFP/PEI complexes not having FOL moieties, and showed far reduced extent of GFP gene inhibition for FOL receptor def...
Park, Tae-Gwanresearcher박태관researcher
한국과학기술원 : 생명과학과,
Issue Date
263433/325007  / 020025814

학위논문(박사) - 한국과학기술원 : 생명과학과, 2007.2, [ x, 117 p. ]


polyelectrolyte complex micelles; gene delivery; cancer therapy; 나노미셀; 유전자 전달; 항암치료

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