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Overcoming multidrug resistance in human tumor cells using free and liposomally encapsulated antisense oligodeoxynucleotides.

Identifieur interne : 004514 ( Main/Exploration ); précédent : 004513; suivant : 004515

Overcoming multidrug resistance in human tumor cells using free and liposomally encapsulated antisense oligodeoxynucleotides.

Auteurs : A R Thierry ; A. Rahman ; A. Dritschilo

Source :

RBID : pubmed:8094959

Descripteurs français

English descriptors

Abstract

Antisense oligonucleotides offer a molecular targeting tool for overcoming cellular multidrug resistance. In order to improve the in vitro and the in vivo transport of oligodeoxynucleotides, we developed a new liposomal delivery system, using the minimal volume entrapment (MVE) technique. We have demonstrated that cellular uptake and intracellular release of oligodeoxynucleotides were facilitated by delivery in liposomes. 15 mers cap phosphorothioate oligodeoxynucleotides complementary to the 5' end of the coding region or to a loop-forming site in the mdr-1 mRNA were encapsulated in liposomes by the MVE method. P-glycoprotein synthesis and doxorubicin resistance were greatly reduced by exposure of the multidrug resistant SKVLB cells to 5 microM liposomally encapsulated oligonucleotide. A lower effect was observed when free oligodeoxynucleotides were used. Oligomers antisense to the loop-forming site appeared to be more effective and more specific in modulating multidrug resistance than oligomers with antisense sequence to the 5' end coding region.

DOI: 10.1006/bbrc.1993.1142
PubMed: 8094959


Affiliations:


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Le document en format XML

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<term>Membrane Glycoproteins (genetics)</term>
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<term>Oligonucleotides, Antisense (administration & dosage)</term>
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<term>Humains</term>
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<term>Oligonucléotides antisens ()</term>
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<term>Résistance aux substances</term>
<term>Séquence nucléotidique</term>
<term>Techniques in vitro</term>
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<term>Oligonucleotides, Antisense</term>
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<div type="abstract" xml:lang="en">Antisense oligonucleotides offer a molecular targeting tool for overcoming cellular multidrug resistance. In order to improve the in vitro and the in vivo transport of oligodeoxynucleotides, we developed a new liposomal delivery system, using the minimal volume entrapment (MVE) technique. We have demonstrated that cellular uptake and intracellular release of oligodeoxynucleotides were facilitated by delivery in liposomes. 15 mers cap phosphorothioate oligodeoxynucleotides complementary to the 5' end of the coding region or to a loop-forming site in the mdr-1 mRNA were encapsulated in liposomes by the MVE method. P-glycoprotein synthesis and doxorubicin resistance were greatly reduced by exposure of the multidrug resistant SKVLB cells to 5 microM liposomally encapsulated oligonucleotide. A lower effect was observed when free oligodeoxynucleotides were used. Oligomers antisense to the loop-forming site appeared to be more effective and more specific in modulating multidrug resistance than oligomers with antisense sequence to the 5' end coding region.</div>
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