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

ABSTRACT

PURPOSE: Certain endothelial cell adhesion molecules are up regulated in tissue that has been irradiated for therapeutic purposes. This up-regulation of adhesion molecules provides a potential avenue for targeting drugs to select tissues. METHODS: Microspheres were coated with a mAb to ICAM-1 and the level of adhesion of the anti-ICAM-1 microspheres to irradiated tissue in vitro and in vivo was quantified. RESULTS: Under in vitro flow conditions, the number of adherent microspheres on irradiated HUVEC was 4.8 +/- 0.9 times that of control; the adhesion of anti-ICAM-1 microspheres on irradiated HUVEC could be enhanced by more than 170% in the presence of RBC (20% hematocrit) in the medium. In vivo in a rat cranial window model, the number of adherent anti-ICAM-1 microspheres in locally irradiated cerebral tissue was 8 and 13 times that of IgG microspheres at 24 h and 48 h post-irradiation, respectively and returned to baseline 7 days post-irradiation. In locally irradiated animals, the number of adhering microspheres in unirradiated tissue remained at the basal level. CONCLUSIONS: Radiation-induced up-regulation of endothelial cell adhesion molecules may be exploited to target drugs and/or genes to select segments of the endothelium.