A microfluidic chip coated with blood vessel cells can show conditions under which nanoparticles accumulate in the plaque-filled arteries of patients with atherosclerosis, the underlying cause of myocardial infarction and stroke.
Researchers from six universities have developed a chip coated with a thin layer of endothelial cells, which make up the interior surface of blood vessels.
The results on the microfluidic device correlated well with nanoparticle accumulation in the arteries of an animal model with atherosclerosis, demonstrating the device's capability to help screen nanoparticles and optimize their design.
"It's a simple model—a microchip, not cell culture dish—which means that a simple endothelialized microchip with microelectrodes can show some yet important prediction of what's happening in a large animal model," said YongTae Kim, an assistant professor in bioengineering in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology.
Kim is part of an international multidisciplinary research team that includes researchers at the David H. Koch Institute for Integrative Cancer Research at MIT, the Icahn School of Medicine at Mount Sinai, the Academic Medical Center in Amsterdam, Kyushu Institute of Technology in Japan, the Boston University School of Medicine and Harvard Medical School.
The U.S. Food and Drug Administration has approved few nanoparticle-based drug delivery systems, compared to proposed studies, said Kim. The entire process developing one nanomedicine platform can take 15 years to go from idea to synthesis to testing in vitro to testing in vivo to approval, according to Kim.
“That's a frustrating process,” Kim said. “Often what works in cell culture dishes doesn't work in animal models.”
Using the microchip, the researchers can create physiologically relevant conditions to cells by altering the rate of blood flow across the cells or by introducing a chemical that is released by the body during inflammation.
"This is a wonderful example of developing a novel nanotechnology approach to address an important medical problem," said Robert Langer, the David H. Koch Institute Professor at MIT, renowned for his work in tissue engineering and drug delivery.
"The work represents a unique integration of microfluidic technology, cardiovascular nanomedicine, vascular biology and in vivo imaging. We now better understand how nanoparticle targeting in atherosclerosis works," said Mark Lobatto of Mount Sinai's Translational and Molecular Imaging Institute.
The research is funded by the National Institutes of Health. Results have been published in the journal Proceedings of the National Academy of Sciences.
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