Dioleoyl phosphatidylethanolamine and PEG–lipid conjugates modify DNA delivery mediated by 1,4-dihydropyridine amphiphiles
Complexes of amphiphilic cationic 1,4-dihydropyridines with DNA (lipoplexes) can be used for nonviral gene delivery. In order to achieve serum-resistant transfection system, DOPE and PEG–lipid conjugates were used to modify 1,4-dihydropyridine amphiphile DHP-12 complexes with DNA. The ability to bin...
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Veröffentlicht in: | Journal of controlled release 2004-09, Vol.99 (1), p.177-190 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Complexes of amphiphilic cationic 1,4-dihydropyridines with DNA (lipoplexes) can be used for nonviral gene delivery. In order to achieve serum-resistant transfection system, DOPE and PEG–lipid conjugates were used to modify 1,4-dihydropyridine amphiphile DHP-12 complexes with DNA. The ability to bind DNA was examined by ethidium bromide displacement assay. Cellular uptake, transfection efficacy and intracellular trafficking of the lipoplexes were assessed using FACS, betagalactosidase gene transfection and confocal laser microscopy, respectively. Cytotoxicity was determined by MTT assay. DHP-12 lipoplexes that included DOPE showed enhanced cell uptake and transfection efficacy both in the absence and presence of serum. PEG–lipid conjugates, in contrast, impaired transfection. In conclusion, combination of DHP-12 with DOPE appears to be a promising transfection system. |
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ISSN: | 0168-3659 1873-4995 |
DOI: | 10.1016/j.jconrel.2004.06.019 |