Targeted Drug Delivery to Endothelial Adhesion Molecules

Figure 3

Enhanced selectivity of targeting to inflamed endothelium of nanocarriers with reduced surface density of ICAM antibody. One way to achieve the targeting nanoparticles (NPs) carrying drugs and probes to precise locations in the body is to couple to the surface of NPs affinity ligands that bind to target molecules. High ligand surface density favors multivalent binding of NPs to target, yet in some cases reduction of ligand density helps to optimize the targeting, as illustrated by detection of the inflamed pulmonary vasculature by isotope-labeled NPs directed to ICAM-1. After intravenous injection in mice, the specific pulmonary uptake of anti-ICAM/carrying NPs directly correlated with NP avidity controlled by ligand surface density. However, in comparison with high-avidity NPs, low avidity NPs exhibited several fold higher selectivity of targeting to the inflamed pulmonary vasculature of endotoxin-challenged versus naive mice. As a result, low avidity NPs provided more selective PET imaging detection of pulmonary vascular inflammation in endotoxin-challenged mice. Computational modeling revealed that the inflammation-induced elevation in surface density of ICAM-1 in the endothelium is critical for multivalent anchoring of NPs with low ligand density, while high-ligand density NPs anchor to both quiescent and inflamed endothelium. From Zern et al. [190].