Hydrophobized dextran-spermine conjugate as potential vector for in vitro gene transfection
| Autor: | Abraham J. Domb, Michal Linial, Hagit Eliyahu, Tony Azzam, A. Makovitzki |
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| Rok vydání: | 2004 |
| Předmět: |
Magnetic Resonance Spectroscopy
Green Fluorescent Proteins Molecular Sequence Data Gene Expression Succinimides Pharmaceutical Science Spermine Biology Gene delivery Transfection Polysaccharide Reductive amination Medicinal chemistry Mice chemistry.chemical_compound Animals Humans Organic chemistry Amines Luciferases chemistry.chemical_classification Drug Carriers Fatty Acids fungi Dextrans DNA beta-Galactosidase Cholesterol Dextran Carbohydrate Sequence chemistry NIH 3T3 Cells Amine gas treating Hydrophobic and Hydrophilic Interactions HeLa Cells Conjugate |
| Zdroj: | Journal of Controlled Release. 96:309-323 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2004.01.022 |
| Popis: | Dextran polysaccharide was grafted by reductive-amination with mixtures of spermine and other natural/synthetic oligoamines of two to four amine groups. The transfection efficiencies of the polycations thus obtained were assessed in various cell lines, and found to depend on the spermine contents. Higher spermine ratios of grafted oligoamines resulted in high gene expression, whereas low to negligible expressions were obtained with lower spermine contents. The effect was explained by spermine residues which exhibit altered buffering capacity in comparison to other substituted oligoamines. Hydrophobization of dextran-spermine (D-SPM) was achieved by treating the polymer with N -hydroxysuccinimide derivatives of cholesterol and fatty acids in a mixture of water/THF. The degree of hydrophobization was in the range of 1–30% mol/mol (hydrophobic moieties/primary amine) and the coupling yields were >95% as determined by 1 H-NMR. The oleate-modified D-SPM remarkably enhanced the gene expression in serum rich media, in marked contrast to unmodified D-SPM which resulted with a drastic decrease in the transfection yields. Modified D-SPM derivatives of other fatty acids and cholesterol showed improved transfection yields in comparison to unmodified D-SPM, but to a lower extent when compared to oleate modification. The improvement in cell transfection was attributed to oleate residues which probably play a role in increasing stability and uptake of polycation–DNA complexes. |
| Databáze: | OpenAIRE |
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