Potential use of polyamidoamine dendrimer/alpha-cyclodextrin conjugate (generation 3, G3) as a novel carrier for short hairpin RNA-expressing plasmid DNA
| Autor: | Hidetoshi Arima, Fumitoshi Hirayama, Toshihito Tsutsumi, Kaneto Uekama |
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| Rok vydání: | 2007 |
| Předmět: |
Dendrimers
alpha-Cyclodextrins Pharmaceutical Science Cell Line Small hairpin RNA chemistry.chemical_compound Mice Microscopy Electron Transmission RNA interference Dendrimer Polyamines Animals Humans Luciferase Particle Size Cytotoxicity Electrophoresis Agar Gel Base Sequence Oligonucleotide Chemistry DNA Molecular biology NIH 3T3 Cells RNA Conjugate Plasmids |
| Zdroj: | Journal of pharmaceutical sciences. 97(8) |
| ISSN: | 1520-6017 |
| Popis: | The potential of starburst® polyamidoamine dendrimer (dendrimer, generation 3, G3) conjugate with α-cyclodextrin (α-CyD) having an average degree of substitution of 2.4 (α-CDE) as a novel carrier of short hairpin RNA (shRNA) expressing plasmid DNA (shpDNA) was evaluated and the shpDNA transfer activity of α-CDE was compared with that of dendrimer (G3). α-CDE formed a stable and condensed complex with shpDNA and induced a conformational transition of shpDNA in solution even in the low charge ratios. In addition, α-CDE markedly inhibited the enzymatic degradation of shpDNA by DNase I. The shpDNA complex with α-CDE at the charge ratio of 20/1 (α-CDE/shpDNA) elicited the most potent RNAi effects in cells transiently and stably expressing the GL3 and GL2 luciferase genes without cytotoxicity among the complexes with the various charge ratios. Besides, the RNAi effects were strikingly enhanced by the further addition of the adequate amounts of siRNA to the shpDNA complex with α-CDE. Taken together, the prominent RNAi effects of the shpDNA complex with α-CDE could be attributed to the stabilizing effect of α-CDE on enzymatic degradation of shpDNA and negligible cytotoxicity. These results suggest that α-CDE possesses the potential to be a novel carrier for shpDNA and siRNA. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3022–3034, 2008 |
| Databáze: | OpenAIRE |
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