%0 Journal Article
%T Targeted Drug Delivery to Endothelial Adhesion Molecules
%A Vladimir R. Muzykantov
%J ISRN Vascular Medicine
%D 2013
%R 10.1155/2013/916254
%X 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¡ªselectins, VCAM-1, PECAM-1, and ICAM-1¡ªrepresent 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. 1. Introduction: Targeting Therapeutics to Endothelium Most therapeutic agents do not naturally accumulate in intended targets in the body, which limits their efficacy and creates issues associated with off-target and systemic side effects and repetitive and complex administration regimens and costs. Utility of many drugs suffers from unfavorable solubility, pharmacokinetics, and permeability across cellular barriers. In order to overcome these issues of pharmacotherapy, drug targeting strategies emerged in the seventies, focusing primarily on delivery of antitumor, antimicrobial, and other toxic agents [1¨C3]. Advances in biotechnology yielded a new type of drugs, biotherapeutics, with wide utilities beyond oncology and infectious diseases, across diverse medical disciplines¡ªcardiology, pulmonology, transplantation, rheumatology, and so forth. These ¡°natural¡± therapeutic agents include recombinant therapeutic proteins including antibodies, enzymes, inhibitors, decoy receptors, as well as diverse nucleic acid formulations¡ªgene therapies, siRNA, miRNA, and so forth. Many of these agents
%U http://www.hindawi.com/journals/isrn.vascular.medicine/2013/916254/