Source:http://linkedlifedata.com/resource/pubmed/id/21071079
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2010-11-26
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pubmed:abstractText |
To improve transfection efficiency and reduce the cytotoxicity of polymeric gene vectors, reducible polycations (RPC) were synthesized from low molecular weight (MW) branched polyethyleneimine (bPEI) via thiolation and oxidation. RPC (RPC-bPEI(0.8 kDa)) possessed MW of 5 kDa-80 kDa, and 50%-70% of the original proton buffering capacity of bPEI(0.8 kDa) was preserved in the final product. The cytotoxicity of RPC-bPEI(0.8 kDa) was 8-19 times less than that of the gold standard of polymeric transfection reagents, bPEI(25 kDa). Although bPEI(0.8 kDa) exhibited poor gene condensing capacities (?2 ?m at a weight ratio (WR) of 40), RPC-bPEI(0.8 kDa) effectively condensed plasmid DNA (pDNA) at a WR of 2. Moreover, RPC-bPEI(0.8 kDa)/pDNA (WR ?2) formed 100-200 nm-sized particles with positively charged surfaces (20-35 mV). In addition, the results of the present study indicated that thiol/polyanions triggered the release of pDNA from RPC-bPEI(0.8 kDa)/pDNA via the fragmentation of RPC-bPEI(0.8 kDa) and ion-exchange. With negligible polyplex-mediated cytotoxicity, the transfection efficiencies of RPC-bPEI(0.8 kDa)/pDNA were approximately 1200-1500-fold greater than that of bPEI(0.8 kDa)/pDNA and were equivalent or superior (?7-fold) to that of bPEI(25 kDa)/pDNA. Interestingly, the distribution of high MW RPC-bPEI(0.8 kDa)/pDNA in the nucleus of the cell was higher than that of low MW RPC-bPEI(0.8 kDa)/pDNA. Thus, the results of the present study suggest that RPC-bPEI(0.8 kDa) has the potential to effectively deliver genetic materials with lower levels of toxicity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Imidoesters,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethyleneimine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/methyl 4-mercaptobutyrimidate,
http://linkedlifedata.com/resource/pubmed/chemical/polycations
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1878-5905
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1193-203
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pubmed:dateRevised |
2011-3-11
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pubmed:meshHeading |
pubmed-meshheading:21071079-Cross-Linking Reagents,
pubmed-meshheading:21071079-Gene Transfer Techniques,
pubmed-meshheading:21071079-Genetic Vectors,
pubmed-meshheading:21071079-HEK293 Cells,
pubmed-meshheading:21071079-Humans,
pubmed-meshheading:21071079-Imidoesters,
pubmed-meshheading:21071079-Materials Testing,
pubmed-meshheading:21071079-Molecular Structure,
pubmed-meshheading:21071079-Molecular Weight,
pubmed-meshheading:21071079-Polyamines,
pubmed-meshheading:21071079-Polyethyleneimine,
pubmed-meshheading:21071079-Sulfhydryl Compounds,
pubmed-meshheading:21071079-Transfection
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pubmed:year |
2011
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pubmed:articleTitle |
A reducible polycationic gene vector derived from thiolated low molecular weight branched polyethyleneimine linked by 2-iminothiolane.
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pubmed:affiliation |
Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara way, Suite 318, Salt Lake City, UT 84108, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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