Targeted Drug Delivery to Endothelial Adhesion Molecules

Endothelial cells represent important targets for therapeutic and diagnostic interventions in many cardiovascular, pulmonary, neurological, inflammatory, and metabolic diseases. Targeted delivery of drugs (especially potent and labile biotherapeutics that require specific subcellular addressing) and imaging probes to endothelium holds promise to improve management of these maladies. In order to achieve this goal, drug cargoes or their carriers including liposomes and polymeric nanoparticles are chemically conjugated or fused using recombinant techniques with affinity ligands of endothelial surface molecules. Cell adhesion molecules, constitutively expressed on the endothelial surface and exposed on the surface of pathologically altered endothelium—selectins, VCAM-1, PECAM-1, and ICAM-1—represent good determinants for such a delivery. In particular, PECAM-1 and ICAM-1 meet criteria of accessibility, safety, and relevance to the (patho)physiological context of treatment of inflammation, ischemia, and thrombosis and offer a unique combination of targeting options including surface anchoring as well as intra- and transcellular targeting, modulated by parameters of the design of drug delivery system and local biological factors including flow and endothelial phenotype. This review includes analysis of these factors and examples of targeting selected classes of therapeutics showing promising results in animal studies, supporting translational potential of these interventions.