Source:http://linkedlifedata.com/resource/pubmed/id/11513800
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2001-8-21
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pubmed:abstractText |
Programmable fusogenic vesicles (PFV) are liposomes composed of non-bilayer lipid components stabilized by the inclusion of an exchangeable poly(ethylene glycol) (PEG)-lipid conjugate. Vesicle destabilization by loss of the PEG-lipid results in recovery of the inherent fusogenic character. As a result, PFV can be designed to display a long circulation lifetime after i.v. administration, high accumulation at disease sites and full bioavailability of an encapsulated compound. In the present study, we investigated the potential application of PFV as carriers for intracellular delivery of antisense oligodeoxynucleotides (ODN). Antisense phosphorothioate ODN were encapsulated into PFV containing dioleoylphosphatidylethanolamine, cholesterol, dioleyldimethylammonium chloride and PEG-ceramides with different carbon chain length (C(8), C(14) and C(20)). In vitro fluorescent microscopy and flow cytometry analysis demonstrated that PFV containing PEG-ceramide C(14) provided enhanced intracellular delivery of FITC-labelled antisense ODN compared to PFV displaying faster or slower rates of destabilization (containing PEG-ceramide C(8) or C(20), respectively). Therapeutic efficacy of PFV-encapsulated antisense ODN against two proto-oncogenes, c-myc and bcl-2, was examined in various cell lines. At antisense concentrations of 0.5 microM, no significant downregulation of c-myc mRNA levels was observed in HEK293, B16 and MCA207 cells. However, treatment of 518A2 melanoma cells with PFV-encapsulated antisense targeting bcl-2 at concentrations of 0.5 microM and 1.0 microM resulted in reduced bcl-2 mRNA level by about 20% and 25% after 48 h incubation. Free antisense ODN did not affect bcl-2 mRNA expression at the concentrations used in this study and encapsulated control antisense (reverse polarity) led to a non-specific increase in mRNA levels. Our results suggest that PFV carriers displaying appropriate rates of destabilization have the potential to act as intracellular delivery vehicles and may improve the bioavailability and potency of antisense oligonucleotides.
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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/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescein-5-isothiocyanate,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
1514
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-13
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11513800-Animals,
pubmed-meshheading:11513800-Cell Line,
pubmed-meshheading:11513800-Cells,
pubmed-meshheading:11513800-Culture Media, Serum-Free,
pubmed-meshheading:11513800-Down-Regulation,
pubmed-meshheading:11513800-Fluorescein-5-isothiocyanate,
pubmed-meshheading:11513800-Fluorescent Dyes,
pubmed-meshheading:11513800-Genes, bcl-2,
pubmed-meshheading:11513800-Genes, myc,
pubmed-meshheading:11513800-Genetic Techniques,
pubmed-meshheading:11513800-Humans,
pubmed-meshheading:11513800-Liposomes,
pubmed-meshheading:11513800-Mice,
pubmed-meshheading:11513800-Oligonucleotides, Antisense,
pubmed-meshheading:11513800-RNA, Messenger,
pubmed-meshheading:11513800-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11513800-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Programmable fusogenic vesicles for intracellular delivery of antisense oligodeoxynucleotides: enhanced cellular uptake and biological effects.
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pubmed:affiliation |
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. qiangh@interchange.ubc.ca
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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