Poly(DMAEMA-NVP)-b-PEG-galactose as gene delivery vector for hepatocytes

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dc.contributor.authorDong Woo Lim-
dc.contributor.authorYoung Il Yeom-
dc.contributor.authorTae Gwan Park-
dc.date.accessioned2017-04-19T08:57:14Z-
dc.date.available2017-04-19T08:57:14Z-
dc.date.issued2000-
dc.identifier.issn1043-1802-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/5168-
dc.description.abstractA block copolymer composed of cationic polymer and poly(ethylene glycol) (PEG) was used as a DNA carrier. Poly(2-(dimethylamino)ethyl methacrylate (DMAEMA)-co-N-vinyl-2-pyrrolidone (NVP)) having a terminal carboxylic group was synthesized by free radical polymerization using an initiator, 4,4'-azobis(4-cyanovaleric acid). The terminal carboxylic acid was activated by N-hydroxysuccinimide (NHS) with dicyclohexylcarbodiimide (DCC) and then conjugated with PEG-bis(amine). For specific gene targeting to asialoglycoprotein receptor of hepatocytes, a galactose moiety was incorporated into the PEG terminal end of poly(DMAEMA-NVP)-b-PEG by reductive coupling using lactose and sodium cyanoborohydride. RSV luciferase plasmid was used as a reporter gene, and in vitro gene transfection efficiency was measured in HepG2 human hepatocarcinoma cells. Poly(DMAEMA-NVP)-b-PEG-galactose/DNA complexes formed at 0.5-2 polymer/plasmid weight ratio had compacted structures around 200 nm particle size and exhibited slightly negative surface charge. These complexes were coated with a cationic, pH sensitive, endosomolytic peptide, KALA, to generate positively charged poly(DMAEMA-NVP)-b-PEG-galactose/DNA/KALA complex particles. In the presence of serum proteins, both the PEG block and the galactose moiety of poly(DMAEMA-NVP)-b-PEG-galactose greatly enhanced the gene transfection efficiency, which was very close to that of Lipofectamine plus. Irrespective of the presence of serum proteins, as the KALA/DNA weight ratio increased, the transfection efficiency of poly(DMAEMA-NVP)-b-PEG-galactose was enhanced due to the pH dependent endosomal disruptive property of KALA. This study demonstrates that sufficient transfection efficiency as high as that of commercial agent could be attained by judicious formulation of molecular engineered poly(DMAEMA-NVP)-b-PEG-galactose in combination with an endosomolytic peptide, KALA.-
dc.publisherAmer Chem Soc-
dc.titlePoly(DMAEMA-NVP)-b-PEG-galactose as gene delivery vector for hepatocytes-
dc.title.alternativePoly(DMAEMA-NVP)-b-PEG-galactose as gene delivery vector for hepatocytes-
dc.typeArticle-
dc.citation.titleBioconjugate Chemistry-
dc.citation.number5-
dc.citation.endPage695-
dc.citation.startPage688-
dc.citation.volume11-
dc.contributor.affiliatedAuthorYoung Il Yeom-
dc.contributor.alternativeName임동우-
dc.contributor.alternativeName염영일-
dc.contributor.alternativeName박태관-
dc.identifier.bibliographicCitationBioconjugate Chemistry, vol. 11, no. 5, pp. 688-695-
dc.identifier.doi10.1021/bc000014u-
dc.description.journalClassY-
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Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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