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

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Abstract
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.

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