Nanomaterials for the Diagnosis and Treatment of Diseases of the Cardiovascular System

Cardiovascular disease (CVD) and its sequelae have been the leading causes of death in the United States for well over two decades. Interestingly, the attention of most researchers skilled in the art of nanomedicine has been disproportionately focused on cancer. This talk will thus focus on the application of nanomaterials to the diagnosis and treatment of several aspects of cardiovascular disease.

Thrombosis is resultant of a number of mechanisms, particularly endothelial damage as is observed in atherosclerotic plaque rupture, or stasis, as can occur on long-haul flights. In all cases, vascular patency correlates well with optimum outcomes. Unfortunately, current classes of thrombolytic drugs possess sub-optimal efficacy and safety profiles, with extraneous bleeding consequences amongst the most deleterious side-effects. Targeted nanomaterials may overcome these limitations by concentrating the drugs at the site of action, potentially decreasing the dose required to bring about a therapeutic effect while concomitantly diminishing side-effects. Nanomaterials can also offer insight into the biology of thrombosis, including inflammation, and the monitoring of thrombus resolution.

Thrombosis within the coronary arteries may result in myocardial infarction (MI) due to the prevention of blood flow to the heart muscle. In worst case scenarios, this results in immediate death. If a patient does survive an MI, there is the potential for eventual heart failure, for which a heart transplant may be necessary. Yet, transplantation is fraught with potential difficulties, including rejection. Whereas clinical monitoring for transplant rejection is extremely invasive, recent research into the development of non-invasive methodologies to monitor this potential pitfall have resulted in a number of imaging agents for the detection of macrophage infiltration and protease activity. More recently, we have developed a fluorogenic nanoagent for the detection of the immune response, namely cytotoxic T lymphocytes. Ultimately, these agents may also prove useful in the monitoring of therapeutic efficacy, particularly the targeted delivery of drug moieties to the heart for the prevention of rejection.