(482b) Nanoparticles Targeting Intercellular Cell Adhesion Molecules

A variety of drug treatments have been investigated in recent decades outlining the potential of targeting specific cytokines or cell adhesion molecules that facilitate leukocyte recruitment. In particular, mAbs can target and bind molecules to disrupt the inflammatory pathway; however, this approach does not allow exclusive disruption of only those cells involved in the localized pathogenesis of the disease. Since the long-term affect of ubiquitous, sustained depression of T-cells and associated cytokines or adhesion molecules has not been studied, side effects such as an increased prevalence of opportunistic infections and/or malignancies are still a concern. As an alternative, nanoparticles may be targeted to ICAM-1, which is drastically up-regulated on the vascular endothelium local to increased production of pro-inflammatory cytokines such as interferon-gamma, interleukin-1-beta, tumor necrosis factor-alpha, etc. Our collaborator, Dr. Teruna Siahaan, has developed a peptide, cLABL (Cyclo(1,12)PenITDGEATDSGC), derived from Leukocyte Function-Associated Factor-1 that binds ICAM-1 with high avidity specificity as an alternative to expensive and immunologically active mAbs. Nanoparticles coated with cLABL peptides are shown to preferentially pool to vascular endothelial cells or other cells (metastasizing cancer cells, activated leukocytes, etc.) exhibiting up-regulated ICAM-1, especially in regions where nanoparticles naturally accumulate (tumors, lungs, liver, etc.). Interestingly, recent studies have indicated that coupling anti-ICAM-1 mAbs to the surface of nanoparticles facilitates internalization of nanoparticles along a novel endocytic route.