Sialyl Lewis(x)-liposomes as vehicles for site-directed, E-selectin-mediated drug transfer into activated endothelial cells.
E-selectin, exclusively expressed on activated endothelial cells, is a potential target for site-directed delivery of agents. We and others have shown that sialyl LewisX-liposomes (sLe(x)-liposomes) are recognized by E-selectin. We now report an approach employing sLe(x)-liposomes to deliver antisense oligonucleotides (AS-ODNs) directed against the adhesion molecule ICAM-1 to activated vascular endothelial cells. ICAM-1 expression was analyzed at the protein level by immunofluorescence and a cell surface ELISA, and at the RNA level by RT-PCR. We have investigated two different AS-ODNs complementary to the 3' untranslated region and the AUG translation initiation codon of ICAM-1 mRNA. Both inhibited protein expression, but did not influence the mRNA level, pointing to a hybridization of AS-ODNs with the mRNA in the cytoplasm. Our results demonstrate the feasibility of a novel approach for the delivery of agents to activated endothelial cells by glycoliposomes targeted to E-selectin.
Max Delbrück Center for Molecular Medicine, Berlin, Germany. renate.stahn@nemod.com
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Stahn
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Grittner
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Zeisig
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Karsten
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Felix
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Wenzel
D002478:Cells, Cultured; D018387:Codon, Initiator / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D009844:Oligosaccharides / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen
D018387:Codon, Initiator; D019040:E-Selectin; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D018799:Intercellular Adhesion Molecule-1