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Emerging Technology and Best Practices Seminar Series
Nanotechnology in Medicine: From Diagnostics to Therapeutics
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Targeted Micro- and Nano-particles for Vulnerable Plaque Detection
Joyce Y. Wong, PH.D
Dept. of Biomedical Engineering
Boston University
Atherosclerotic disease, characterized by plaque formation in the arteries, remains the leading cause of death in the Western world. It can be a ‘silent-killer’ because undetected plaques can rupture without warning (“vulnerable”plaque), and result in a blood clot within the artery (atherothrombosis) causing a myocardial infarction and stroke. In the U.S. alone, heart attacks strike 1.1 million people each year. The incidence of atherosclerotic vascular disease is also increasing proportionately with the observed increase in incidence of obesity and type-2 diabetes. While the gold standard for diagnosing the presence of atherosclerotic disease is invasive angiography (cardiac catheterization), this method cannot distinguish between stable and vulnerable plaque prior to an atherothrombotic event, nor can it detect the non-flow limiting and clinically silent plaques that often rupture. Currently, no method exists today that can reliably detect vulnerable plaque in the human vascular system (in vivo).
A major challenge in developing clinically-useful drug carriers or imaging contrast agents lies in achieving specific binding with intended targets while at the same time avoiding recognition by the immune system. Targeted delivery of therapeutics would greatly impact the pharmaceutical industry by allowing the use of drugs currently shelved because of detrimental side effects. Equally as important, the development of targeted contrast agents would greatly facilitate early detection of disease. Traditionally carriers have been tested in either animal models or cell culture static binding studies. Here we describe a model in vitro system to investigate how physiologically-relevant PEGylation conditions (5 mol% polyethylene glycol) affect carrier binding properties under flow. Physiological flow is a critical parameter that impacts targeting because of the natural variation of flow in the different types of arteries and veins in the circulation.
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