Evaluation of cationic assemblies constructed with amino acid based lipids for plasmid DNA delivery.
We synthesized cationic lipids bearing lysine, histidine, or arginine as a cationic headgroup for use in gene transfer studies. The cationic assemblies formed from lysine- or arginine-type lipids gave unilamellar vesicles (approximately 100 nm diameter), whereas the morphology of the histidine-type lipids was tube-like. The competences of the cationic assemblies were sufficient to form lipoplexes, and the resulting lipoplexes were evaluated in terms of gene expression efficiencies with COS-7 cells. The lysine- or arginine-type lipids exhibited higher gene expression efficiencies than that of Lipofectamine2000, a conventional transgenic reagent, indicating that stable lipoplexes could be prepared between spherical cationic assemblies and plasmid DNA. The gene expression efficiency in relation to the cationic headgroup of the lipids was as follows: lysine > or = arginine > histidine. In addition, gene expression efficiency was enhanced by decreasing the length of the alkyl chain of the hydrophobic moiety. Unlike Lipofectamine2000, no reduction in transfection efficiency in the presence of fetal bovine serum was observed for the lipoplexes formed using synthetic cationic lipids. Moreover, the synthetic cationic lipids revealed remarkably low cytotoxicity compared with Lipofectamine2000. In conclusion, cationic assemblies formed from 1,5-ditetradecyl-N-lysyl-L-glutamate or 1,5-ditetradecyl-N-arginyl-L-glutamate can be used as an effective plasmid DNA delivery system.
Obata
Yosuke
Y
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
Suzuki
Daisuke
D
Takeoka
Shinji
S
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics; D005312:Fetal Blood / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010957:Plasmids / Q000737:chemistry*; D013997:Time Factors
D000596:Amino Acids; D002412:Cations; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D004247:DNA