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  Structural variation of cationic lipids: minimum requirement for improved oligonucleotide delivery into cells

Lindner, L. H., Brock, R., Arndt-Jovin, D. J., & Eibl, H. (2006). Structural variation of cationic lipids: minimum requirement for improved oligonucleotide delivery into cells. Journal of Controlled Release, 110(2): 10.1016/j.jconrel.2005.10.009, pp. 444-456. Retrieved from http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T3D-4HK5SG2-6-R&_cdi=4944&_user=38661&_orig=search&_coverDate=01%2F10%2F2006&_sk=998899997&view=c&wchp=dGLzVtb-zSkWz&md5=01be42df58bf5f0afde9239578a03c02&ie=/sdarticle.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-E57C-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-DCBE-C
Genre: Journal Article

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 Creators:
Lindner, L. H., Author
Brock, R.1, Author              
Arndt-Jovin, D. J.2, Author
Eibl, H.3, Author              
Affiliations:
1Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              
2Max Planck Society, ou_persistent13              
3Research Group of Phospholipids, MPI for biophysical chemistry, Max Planck Society, ou_578562              

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Free keywords: cationic lipids; transfection; lipid-DNA complexes; serum resistance
 Abstract: In vivo transfection efficiency (TE) using cationic liposome/oligonucleotide (ODN) complexes is often hampered by interactions with serum components. Novel cationic lipids with different hydroxyethyl or dihydroxypropyl ammonium backbones, esterified hydrocarbon chains and hydroxy substituents have been synthesized and applied in cationic liposome formulations with and without the helper lipid DOPE (1:1, m/m). Their properties for cellular ODN delivery were determined using fluorescently labeled ODNs (F-ODNs). Cationic lipids with hydrocarbon chains esterified to non-glycerol backbones in non-vicinal configuration were completely ineffective in nuclear ODN-delivery. Instead, an increased cytoplasmic localization of F-ODNs was observed. Cationic lipids equipped with only one hydrocarbon were completely incompetent for cellular ODN delivery. In the absence of serum, all cationic lipids tested with hydrocarbon chains in vicinal configuration esterified to a glycerol backbone (the respective N-(1,2-diacyl-dihydroxypropyl)-N,N,N-trimethyl-ammoniumchlorides or N-(1,2-diacyl-dihydroxypropyl)-N(hydroxyethyl)-N,N-dimethyl-ammoniumchlorides as well as N-(1,2-diacyl-dihydroxypropyl)-N(1,2-dihydroxypropyl)-N,N-dimethyl-ammoniumchlorides with lauroyl, myristoyl, palmitoyl, stearoyl and erucoyl chains) were able to transfect cells when combined with DOPE (20–80% nuclear fluorescence). Remarkably, only the analog esterified with two myristoyl chains was equally effective even in the absence of DOPE. By adding hydroxy groups to the N-alkyl residue, TE under serum conditions was improved yielding transfection rates of 55%, 75% and 90% for 0, 1 or 2 substituted hydroxy groups, respectively. For plasmid DNA, different requirements were identified. Again, the analog with two myristoyl chains was most effective but only in the presence of DOPE. However, the addition of hydroxy groups had no influence on the TE in the presence of serum.

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Language(s): eng - English
 Dates: 2005-10-122006-01-10
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Journal of Controlled Release
Source Genre: Journal
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Pages: - Volume / Issue: 110 (2) Sequence Number: 10.1016/j.jconrel.2005.10.009 Start / End Page: 444 - 456 Identifier: -