Targeting microparticles to select tissue via radiation induced upregulation of endothelial cell adhesion molecules

摘要

The up-regulation of certain endothelial cell adhesion molecules in tissue that has been irradiated for therapeutic purposes provides a potential avenue for targeting drugs to select tissue. Microspheres were coated with a mAb to ICAM-l and the level of adhesion of the anti-ICAM-l microspheres to irradiated tissue in vitro and in vivo was quantified. Under in vitro flow conditions, the number of adherent microspheres on irradiated HUVEC was 4.5±0.9 times that of control; this ratio could be enhanced by increasing ligand density on the surface of the microspheres, adding RBC to the suspending media, or reducing shear rate. In vivo in a rat cranial window model, the number of adherent anti-ICAM-1 microspheres in irradiated cerebral tissue was 13 times that of IgG microspheres at 48hr post-irradiation. In locally irradiated animals, the number of adhering microspheres in unirradiated tissue remained at the basal level.