Enhancing Effects of Galactosylated Dendrimer/.ALPHA.-Cyclodextrin Conjugates on Gene Transfer Efficiency
| Autor: | Fumitoshi Hirayama, Toshihito Tsutsumi, Koki Wada, Hidetoshi Arima, Kaneto Uekama |
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| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
alpha-Cyclodextrins Cell Survival Gene Transfer Techniques Galactose Pharmaceutical Science General Medicine Transfection Gene delivery In vitro Mice chemistry.chemical_compound chemistry Biochemistry Cell Line Tumor Dendrimer NIH 3T3 Cells Animals Humans Agarose Asialoglycoprotein receptor Cytotoxicity Conjugate |
| Zdroj: | Biological and Pharmaceutical Bulletin. 28:500-505 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.28.500 |
| Popis: | To improve in vitro gene transfer efficiency and/or achieve cell-specific gene delivery of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2) conjugate with alpha-cyclodextrin (alpha-CDE conjugate (G2)), we prepared alpha-CDE conjugate bearing galactose (Gal-alpha-CDE conjugates) with the various degrees of substitution of the galactose moiety (DSG) as a novel non-viral vector. The agarose gel electrophoretic studies revealed that Gal-alpha-CDE conjugates formed complexes with plasmid DNA (pDNA) and protected the degradation of pDNA by DNase I, but these effects impaired as the DSG value increased. Dendrimer and alpha-CDE conjugate exerted pDNA condensation through the complexation, but Gal-alpha-CDE conjugates did not. Gal-alpha-CDE conjugate (DSG 4) was found to have much higher gene transfer activity than dendrimer, alpha-CDE conjugate and Gal-alpha-CDE conjugates (DSG 8, 15) in HepG2, NIH3T3 and A549 cells, which are independent of the expression of the asialoglycoprotein receptor. Transfection activity of Gal-alpha-CDE conjugate (DSG 4) was insensitive to the existence of competitors (asialofetuin and galactose) and serum. In addition, no cytotoxicity after transfection of the complex of pDNA with Gal-alpha-CDE conjugate (DSG 4) was observed. These results suggest the potential use of Gal-alpha-CDE conjugate (DSG 4) as a non-viral vector in various cells. |
| Databáze: | OpenAIRE |
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