Nanoparticle-based targeted delivery of therapeutics and non-invasive imaging of unstable endothelium

Transluminal coronary angioplasty (percutaneous transluminal coronary angioplasty; PTCA) was introduced in the late 1970s as a non-surgical treatment for obstructive coronary artery disease and blockage due to myocardial infarction (MI). The procedure involves placing a balloontipped catheter at the site of occlusion and disrupting and expanding the occluded vessel by inflating the balloon. Although initially successful at removal of the blockage and luminal enlargement, the process also damages the blood vessel wall extensively, including the loss of the endothelial lining. An ensuing response to this severe injury is often enhanced expression of cytokines and growth factors, and subsequently, a rapid acute reclosure and/or a slow progressive reocclusion or restenosis of the vessel. Within the vascular wall, this response typically includes myointimal hyperplasia, proliferation of smooth muscle cells and fibroblasts, connective tissue matrix remodeling, and formation of thrombus. Restenosis, referring to the renarrowing of the vascular lumen following an intervention such as balloon angioplasty, is clinically defined as a >50% loss of the initial luminal diameter gain following the interventional procedure and has affected anywhere from 25 to 35% of treated patients.1,2 Today, standard therapy for MI or other luminal narrowing includes thrombolytics, anticoagulants, and often, interventional procedures such as PTCA. Recently, an advance to the procedure has been the introduction of stents, metallic-based cage/tube-like structures placed into the vessel lumen with PTCA, and the rate of acute reclosure has been minimized. Coronary stents provide luminal scaffolding, eliminating elastic recoil and remodeling which can occur rapidly following an interventional procedure. Unfortunately, however, although the occurrence of acute reclosure was reduced, there was actually no decrease in neointimal hyperplasia, and in fact, the procedure led to an increase in the proliferative component of restenosis and a relatively higher rate of reocclusion and need for reintervention often as early as 3 months to 1 year following the procedure.3.