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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-1-21
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pubmed:abstractText |
Brain capillary endothelial cells of the blood-brain barrier (BBB) are difficult targets for nonviral transfection even for the most potent transfection agents. Efficient protection and nuclear delivery of plasmid DNA are the key requirements for enhancing the transfection. We designed novel DNA intercalating conjugates of PEG-tris(acridine) with a short nuclear localization signal (NLS) peptide and investigated the effect of their complexes with luciferase-encoded plasmid DNA on lipoplex- and polyplex-mediated transfection of murine brain capillary endothelial bEnd.3 cells. These intercalation complexes protected DNA from nucleolytic degradation forming a protective PEG layer around plasmid DNA and could be efficiently condensed by Lipofectamine2000 or Exgen500 into nanosized particles. Complexation of plasmid DNA with a PEG-acridine/NLS-PEG-acridine mixture (9:1 w/w), taken in an amount equal to 5-6 NLS peptides per DNA molecule, significantly enhanced both lipo- and polyplex transfection efficacies and increased the number of transfected bEnd.3 endothelial cells in the presence of serum. Comparative transgene expression efficiency was significantly higher at longer PEG linker and optimal conjugate-to-DNA weight ratio, especially, at lower N/P ratio for both transfection agents, reaching 15-16-fold for lipoplexes and 10-11-fold for polyplexes. In addition, the NLS-PEG-acridine conjugates did not increase cytotoxicity of lipoplexes and polyplexes to bEnd.3 cells. These conjugates can serve as promising components for development of systemic nonviral transfecting approach to the transfection of the BBB and temporary modulation of its drug permeability.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-10022527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-10429244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-10694822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-11708884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-11731785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-12409265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-12468221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-12612647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-14568334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-16173787,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-16225967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17287293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17327830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17440069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17454356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17584788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17619998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17680778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17681634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-17979652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-2831963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-7642560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-9447599,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19067581-9874777
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1520-4812
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
120-8
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19067581-Acridines,
pubmed-meshheading:19067581-Animals,
pubmed-meshheading:19067581-Blood-Brain Barrier,
pubmed-meshheading:19067581-Brain,
pubmed-meshheading:19067581-Cell Line,
pubmed-meshheading:19067581-Cell Nucleus,
pubmed-meshheading:19067581-Drug Delivery Systems,
pubmed-meshheading:19067581-Endothelial Cells,
pubmed-meshheading:19067581-Mice,
pubmed-meshheading:19067581-Nuclear Localization Signals,
pubmed-meshheading:19067581-Polyethylene Glycols,
pubmed-meshheading:19067581-Transfection
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pubmed:year |
2009
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pubmed:articleTitle |
Efficient transfection of blood-brain barrier endothelial cells by lipoplexes and polyplexes in the presence of nuclear targeting NLS-PEG-acridine conjugates.
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pubmed:affiliation |
Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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