Enhancement of gene expression by polyamidoamine dendrimer conjugates withalpha-, beta-, and gamma-cyclodextrins

To improve the transfection efficiency of nonviral vector, we synthesized t he starburst polyamidoamine dendrimer conjugates with alpha-, beta-, and ga mma -cyclodextrins (CDE conjugates), expecting the synergistic effect of de ndrimer and cyclodextrins (CyDs). The H-1 NMR spectroscopic data indicated that alpha-, beta-, and gamma -CyDs are covalently bound to dendrimer in a molar ratio of 1:1. The agarose gel electrophoretic studies revealed that C DE conjugates formed the complexes with plasmid DNA (pDNA) and protected th e degradation of pDNA by DNase I in the same manner as dendrimer. CDE conju gates showed a potent luciferase gene expression, especially in the dendrim er conjugate with alpha -CyD (alpha -CDE conjugate) which provided the grea test transfection activity (approximately 100 times higher than those of de ndrimer alone and of the physical mixture of dendrimer and alpha -CyD) in N IH3T3 and R4W264.7 cells. In addition, the gene transfer activity of alpha -CDE conjugate was superior to that of Lipofectin. The enhancing gene trans fer effect of alpha -CDE conjugate may be attributable to not only increasi ng the cellular association, but also changing the intracellular traffickin g of pDNA. These findings suggest that alpha -CDE conjugate could be a new preferable nonviral vector of pDNA.