Source:http://linkedlifedata.com/resource/pubmed/id/15506170
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2004-10-27
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| pubmed:abstractText |
The purpose of this research is to develop ligand-targeted plasmid based gene delivery systems for gene transfer to tumor endothelium. Cell adhesion assays were used to test the peptide inhibition of human endothelial cell adsorption to vitronectin-treated tissue culture plates. A series of RGD containing peptides were tested in linear form and with one and two disulfide bonds. The linear and two disulfide bond peptides yielded similar IC50 (approximately 1 x 10(-7) M). Substitution of two methionines for cysteines yielded a single disulfide bond that increased the IC50 by 10-fold. The single and double disulfide peptides were derivatized to N-succinyl-dioleoylphopsphatidylethanolamine and incorporated into 100 nm liposomes radiolabeled with H-cholesterylhexadecylether. Liposome uptake by human umbilical vein endothelial cells was tested as a function of lipopeptide surface density. Increase in membrane surface density from 5 to 20mol% increased human umbilical derived endothelial cell (HUVEC) uptake of the liposomes for both the single and double disulfide peptides. Liposome uptake by HUVECs was 3-fold greater for the double disulfide compared to the single disulfide. The single and double disulfide lipopeptides were then tested for gene transfer to HUVECs using DOTMA:Cholesterol cationic liposomes. The polyplexes were formed by rapidly mixing plasmid DNA with DOTMA:CHOL liposomes at a 3:1 charge ratio in 2% ethanol, 10% lactose. The ethanol was removed by lyophilization and upon rehydration, the lipoplexes had a mean diameter of approximately 100nm. HUVEC transfection studies showed that increasing the mol% of the single disulfide RGD lipopeptide to 20mol% increased gene transfer by 10-fold. This increase in transfection could be reduced to that obtained in the absence of lipopeptide by co-incubating the HUVECs with a 100-fold excess of the single disulfide RGD peptide, thus demonstrating lipopeptide mediated gene transfer to endothelial cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cations,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alphaVbeta3,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/N-(1-(2,3-dioleyloxy)propyl)-N,N,N-t...,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/arginyl-glycyl-aspartic acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1061-186X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
12
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
215-21
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| pubmed:dateRevised |
2006-5-1
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| pubmed:meshHeading |
pubmed-meshheading:15506170-Cations,
pubmed-meshheading:15506170-Cell Adhesion,
pubmed-meshheading:15506170-Cholesterol,
pubmed-meshheading:15506170-Disulfides,
pubmed-meshheading:15506170-Endothelial Cells,
pubmed-meshheading:15506170-Endothelium, Vascular,
pubmed-meshheading:15506170-Gene Transfer Techniques,
pubmed-meshheading:15506170-Humans,
pubmed-meshheading:15506170-Integrin alphaVbeta3,
pubmed-meshheading:15506170-Ligands,
pubmed-meshheading:15506170-Liposomes,
pubmed-meshheading:15506170-Luciferases,
pubmed-meshheading:15506170-Oligopeptides,
pubmed-meshheading:15506170-Peptides,
pubmed-meshheading:15506170-Plasmids,
pubmed-meshheading:15506170-Quaternary Ammonium Compounds,
pubmed-meshheading:15506170-Transfection,
pubmed-meshheading:15506170-Umbilical Veins
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| pubmed:year |
2004
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| pubmed:articleTitle |
Peptide-mediated gene transfer of cationic lipid/plasmid DNA complexes to endothelial cells.
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| pubmed:affiliation |
Expression Genetics, Huntsville, AL, USA.
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| pubmed:publicationType |
Journal Article
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