Scientists have engineered a microchip coated with blood vessel cells to learn more about the conditions under which nanoparticles accumulate in the plaque-filled arteries of patients with atherosclerosis – the underlying cause of myocardial infarction and stroke.
In the research, microchips were coated with a thin layer of endothelial cells, which make up the interior surface of blood vessels. In healthy blood vessels, endothelial cells act as a barrier to keep foreign objects out of the bloodstream. However, at sites prone to atherosclerosis, the endothelial barrier breaks down, allowing things to move in and out of arteries that shouldn’t.
In a new study, nanoparticles were able to cross the endothelial cell layer on the microchip under conditions that mimic the permeable layer in atherosclerosis. 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 important predictions of what’s happening in a large animal model,” said YongTae (Tony) Kim, an assistant professor in bioengineering in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology.
This work represents a multidisciplinary effort of researchers that are collaborating within the Program of Excellence in Nanotechnology funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health (NIH). The team includes researchers at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (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.
“This is a wonderful example of developing a novel nanotechnology approach to address an important medical problem,” says Robert Langer, the David H. Koch Institute Professor at MIT, who is renowned for his work in tissue engineering and drug delivery.
Kim and Langer teamed up with researchers from the Icahn school in New York – Mark Lobatto, co-lead author works in the laboratories of Willem Mulder, an expert in cardiovascular nanomedicine, and Zahi Fayad, the director of Mount Sinai’s Translational and Molecular Imaging Institute.
The researchers hope that their microchip can accelerate the nanomedicine development process by better predicting therapeutic nanoparticles’ performance in larger animal models, such as rabbits. Such a complementary in vitro model would save time and money and require fewer animals.
Few nanoparticle-based drug delivery systems have been approved by the U.S. Food and Drug Administration (FDA), Kim says. The entire process of developing one nanomedicine platform can take 15 years to go from idea to synthesis to testing in vitro to testing in vivo to approval.
“That’s a frustrating process,” Kim states. “Often what works in cell culture dishes doesn’t work in animal models.”
To help speed up nanomedicine research by improving the predictive capabilities of in vitro testing, Kim and colleagues designed their microchip to mimic what goes on in the body better than what is currently possible through routine cell culture.
“In the future, we can make microchips that are much more similar to what’s going on in animal models, or even human beings, compared to the conventional cell culture dish studies,” Kim states.
Georgia Institute of Technology
Photo credit: YongTae (Tony) Kim/PNAS.