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pubmed-article:10721798pubmed:abstractTextWe have investigated the intracellular fate and antisense effect of oligonucleotide/cationic liposome complexes using phosphorothioate oligonucleotides (S-Oligo) targeted to inducible nitric oxide synthase in mouse peritoneal macrophages. Confocal laser microscopic analysis revealed that, after application of fluorescein isothiocyanate (FITC)-labeled S-Oligo alone, the intracellular localization of fluorescence exhibited a punctate pattern in the cytoplasm, suggesting that the oligonucleotides were mainly confined to the endosomal and/or lysosomal compartments. In the case of complexation with Lipofectin and DMRIE-C liposomes, cellular uptake of FITC-S-Oligo was not greatly enhanced and the fluorescence localization in the cells was similar to that of FITC-S-Oligo alone. LipofectAMINE slightly enhanced cellular uptake of FITC-S-Oligo; however, the intracellular localization profile of FITC-S-Oligo remained largely unchanged. The antisense effect was slightly enhanced by LipofectAMINE under only very limited experimental conditions. It was concluded that cationic liposomes are not a potential carrier for S-Oligo in peritoneal macrophages because of their inability to promote the release of S-Oligo from the endosomal compartments to the cytosol over a non-toxic concentration range.lld:pubmed
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pubmed-article:10721798pubmed:pagination363-71lld:pubmed
pubmed-article:10721798pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:10721798pubmed:articleTitleEffect of cationic liposomes on intracellular trafficking and efficacy of antisense oligonucleotides in mouse peritoneal macrophages.lld:pubmed
pubmed-article:10721798pubmed:affiliationDepartment of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.lld:pubmed
pubmed-article:10721798pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10721798pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed