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 pote ntial target for site-directed delivery of agents. We and others have shown that sialyl Lewis(x)-liposomes (sLe(x)-liposomes) are recognized by E-sele ctin. We now report an approach employing sLe(x)-liposomes to deliver antis ense 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 comple mentary to the 3' untranslated region and the AUG translation initiation co don of ICAM-1 mRNA. Both inhibited protein expression, but did not influenc e the mRNA level, pointing to a hybridization of AS-ODNs with the mRNA in t he cytoplasm. Our results demonstrate the feasibility of a novel approach f or the delivery of agents to activated endothelial cells by glycoliposomes targeted to E-selectin.