Intercellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein and coreceptor for leukocyte integrins, is overexpressed in inflammation, thrombosis, oxidative stress, metabolic diseases, and various genetic conditions; therefore, ICAM-1 represents a target for delivery of drug carriers to areas affected by disease. To mitigate the obstacles of long-term use of antibody-coated nanocarriers for treatment, Garnacho et al. evaluated polymer nanocarriers targeted to ICAM-1 by a 17-mer linear peptide derived from the ICAM-1-binding sequence of fibrinogen, γ3. These results show that γ3 nanocarriers target ICAM-1 with efficiency and specificity similar to that of anti-ICAM nanocarriers. Furthermore, γ3 nanocarriers are internalized by cells in culture and in vivo and transported to lysosomes via cell adhesion molecule (CAM)-mediated endocytosis, without apparent disruption of cell junctions, similar to anti-ICAM counterparts. These results show that model polymer nanocarriers coated with γ3 efficiently and specifically bind to both human and mouse ICAM-1. This provides targeting and intracellular transport similar to that of anti-ICAM NCs previously reported, offering a new opportunity to advance the design of translational ICAM-1-targeting platforms in the preclinical and, perhaps, future clinical realm.
See article at J Pharmacol Exp Ther 2012, 340:638–647.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics