Enhancement of Gene Expression by Polyamidoamine Dendrimer Conjugates with α-, β-, and γ-Cyclodextrins

To improve the transfection efficiency of nonviral vector, we synthesized the starburst polyamidoamine dendrimer conjugates with α-, β-, and γ-cyclodextrins (CDE conjugates), expecting the synergistic effect of dendrimer and cyclodextrins (CyDs). The 1H NMR spectroscopic data indicated that α-, β-,...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2001-07, Vol.12 (4), p.476-484
Main Authors: Arima, Hidetoshi, Kihara, Fumihiro, Hirayama, Fumitoshi, Uekama, Kaneto
Format: Article
Language:English
Subjects:
3T3 Cells - metabolism
Animals
Binding Sites - physiology
Cyclodextrins - chemistry
Cyclodextrins - pharmacology
Deoxyribonuclease I - metabolism
DNA - chemistry
DNA - metabolism
Drug Synergism
Gene Expression - drug effects
Gene Transfer Techniques
Genetic Vectors - genetics
Mice
Microscopy, Confocal
Phosphatidylethanolamines - pharmacology
Plasmids - chemistry
Polymers - pharmacology
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To improve the transfection efficiency of nonviral vector, we synthesized the starburst polyamidoamine dendrimer conjugates with α-, β-, and γ-cyclodextrins (CDE conjugates), expecting the synergistic effect of dendrimer and cyclodextrins (CyDs). The 1H NMR spectroscopic data indicated that α-, β-, and γ-CyDs are covalently bound to dendrimer in a molar ratio of 1:1. The agarose gel electrophoretic studies revealed that CDE conjugates formed the complexes with plasmid DNA (pDNA) and protected the degradation of pDNA by DNase I in the same manner as dendrimer. CDE conjugates showed a potent luciferase gene expression, especially in the dendrimer conjugate with α-CyD (α-CDE conjugate) which provided the greatest transfection activity (approximately 100 times higher than those of dendrimer alone and of the physical mixture of dendrimer and α-CyD) in NIH3T3 and RAW264.7 cells. In addition, the gene transfer activity of α-CDE conjugate was superior to that of Lipofectin. The enhancing gene transfer effect of α-CDE conjugate may be attributable to not only increasing the cellular association, but also changing the intracellular trafficking of pDNA. These findings suggest that α-CDE conjugate could be a new preferable nonviral vector of pDNA.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc000111n