The aim of this study was to evaluate the potential of different types of
sialyl Lewis X-conjugated
liposomes as competitive inhibitors for tumour cell adhesion to endothelial
E-selectin. Sterically stabilised
liposomes with the sLeX
ligand at the terminal end of the polyethyleneglycol (PEG) chain, as well as vesicles that had the
ligand embedded within the PEG-layer, were compared to
ligand-bearing
liposomes without sterical stabilisation. First, 14 different tumour cell lines were characterised for their expression of
sialyl Lewis X and/or A. Tumour cell adhesion was characterised in three static assays in vitro using: (i) immobilised
E-selectin, (ii) CHO cells, transfected to express
E-selectin and (iii) human umbilical vein endothelial cells (HUVEC). Sterically stabilised
liposomes with the
ligand at the terminal end of the
polyethylene chain were the most effective inhibitors in all three assays and inhibited the adhesion of HT29 colon- and Lewis lung (LL)
carcinoma cells by about 60-80%. The binding was not affected by a PEG-coating of the
liposomes. Sterical stabilisation, on the other hand, completely prevented macrophage uptake (J774 cell line) independently of the presence of the
ligand, while plain
liposomes were taken up in an amount of 5.4 nmol liposomal
lipids/10(6) macrophages.