Effects of structure of polyamidoamine dendrimer on gene transfer efficiency of the dendrimer conjugate with alpha-cyclodextrin
| Autor: | Toshihito Tsutsumi, Kaneto Uekama, Hidetoshi Arima, Fumihiro Kihara, Fumitoshi Hirayama |
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| Rok vydání: | 2002 |
| Předmět: |
alpha-Cyclodextrins
Stereochemistry Polymers alpha-Cyclodextrin Static Electricity Biomedical Engineering Pharmaceutical Science Gene Expression Bioengineering Transfection chemistry.chemical_compound Mice Dendrimer Static electricity Tumor Cells Cultured Animals Deoxyribonuclease I Particle Size Pharmacology chemistry.chemical_classification Cyclodextrins Drug Carriers Cyclodextrin Organic Chemistry Biological membrane Biological Transport 3T3 Cells DNA Fluorescence chemistry Biophysics Biotechnology Conjugate |
| Zdroj: | Bioconjugate chemistry. 13(6) |
| ISSN: | 1043-1802 |
| Popis: | To improve gene transfer activity of a new nonviral vector, a polyamidoamine dendrimer (G2) conjugate with alpha-cyclodextrin (alpha-CDE conjugate (G2)), we prepared alpha-CDE conjugates with dendrimer having different generations (G3 and G4), and their gene transfer activities were compared with those of alpha-CDE conjugate (G2) and TransFast, a novel transfection reagent. alpha-CDE conjugates (G2, G3, and G4) formed the complexes with pDNA, changing the zeta-potential and particle size of pDNA complexes and the protection of pDNA from DNase I in a charge ratio-dependent manner, although their differences at higher charge ratios (vector/pDNA) were small. The gene transfer activity of alpha-CDE conjugates (G2, G3, and G4) was higher than that of the corresponding dendrimer alone in NIH3T3 and RAW264.7 cells. Of these CDE conjugates, alpha-CDE conjugate (G3) had a superior gene transfer activity which was comparable to that of TransFast in NIH3T3 cells. The intracellular distribution of pDNA after application of the pDNA complex with alpha-CDE conjugate (G3) to NIH3T3 cells was different from that with dendrimer alone (G3), although the cellular association of pDNA was almost comparable among all vectors. alpha-CDE conjugate (G3) strongly interacted with a fluorescence probe, 2-(p-toluidinyl)-naphthalene-6-sulfonate (TNS), suggesting that the conjugate possesses the inclusion ability with biomembrane constituents such as phospholipids after transfection. These results suggest that alpha-CDE conjugates, particularly the G3 conjugate, could be novel nonviral gene transfer agents. |
| Databáze: | OpenAIRE |
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