期刊
CHEMBIOCHEM
卷 9, 期 9, 页码 1462-1471出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200700727
关键词
cationic lipids; imidazolium; lipoplexes; liposomes; nonviral gene transfer; phosphoramidate
In an effort to enhance the gene-transfer efficiencies of cationic lipids and to decrease their toxicities, a series of new phosphoramidate lipids with chemical similarity to cell membrane phospholipids was synthesised. These lipids contained various cationic headgroups, such as arginine methyl ester, lysine methyl ester, homoarginine methyl ester, ethylenediamine, diaminopropane, guanidinium and imidazolium. Their transfection abilities, either alone or with the co-lipid DOPE, were evaluated in HEK293-T7 cells. We found that imidazolium lipophosphoramidate 7a/DOPE lipoplexes gave the most efficient transfection with low toxicity (75916). The luciferase activity was 100 times higher than that obtained with DOTAP/DOPE lipoplexes. The size, zeta potential, pDNA-liposome interactions and cellular uptakes of the lipoplexes were determined. No definitive correlation between the zeta potential values and the transfection efficiencies could be established, but the uptake of lipoplexes by the cells was correlated with their final transfection efficiencies. Our results show that imidazolium phosphoramidate lipids constitute a potential new class of cationic lipids for gene transfer.
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