Table of Contents
Air Pollution, Nanomedicine Particles
Linked to Blood Clotting
Research findings indicate need for caution in medical applications of nanotechnology
Carbon nanoparticles – both those unleashed in the air by engine exhaust and the engineered structures thought to have great potential in medical applications – promote blood-clotting, scientists reported in a September online edition of the British Journal of Pharmacology.
Anna Radomski, M.D., and Marek Radomski, M.D., Ph.D., check
blood platelets for aggregation - forming blood clots - in the
presence of nanoparticles. This unexpected effect of
nanoparticles was found in research at the Brown Foundation
Institute of Molecular Medicine for the Prevention of Human
Diseases. Photo by Ester Fant
Researchers from The University of Texas Health Science Center at Houston and Ohio University examined the impact of various forms of carbon nanoparticles in a laboratory experiment on human platelets – blood’s principal clotting element – and in a model of carotid artery thrombosis, or blockage, using anesthetized rats.
“We found that some carbon nanoparticles activate human platelets and stimulate them to aggregate, or clump together. We also demonstrated that the same nanoparticles stimulated blockage of the carotid artery in the rat model,” said research team leader Marek Radomski, M.D., Ph.D., of the Center for Vascular Biology at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) at the UT Health Science Center.
C60, a spherical carbon molecule also known as a fullerene or “bucky ball,” was the exception, showing no effect on human platelet aggregation and very little effect on rat thrombosis.
“This research is not a case against nanotechnology. It’s difficult to overestimate the importance of this amazing technology’s ability to transform medicine. But it’s good to assess the risk of a new technology in advance. This is a case for moving ahead in a cautious and informed way,” said Radomski, who also is a professor of integrative biology and pharmacology at the UT Medical School at Houston.
Nanoparticles – so tiny that they are measured in billionths of a meter – pass easily through the lungs and into the bloodstream, Radomski said, where they can interact with platelets. They also tend to aggregate on their own, a property that also could enhance blood clotting.
“Medical evidence has been accumulating mainly from epidemiological studies that exposure of humans to particulate matter, and to very small particles, increases the risk of cardiovascular disease,” Radomski said. “The mechanisms of that risk are not well-known. Clot formation is my research interest, and we wanted to look at the effect of nanoparticles – both the pollutants caused by combustion and engineered nanoparticles that might be used in various nanomedical devices, such as improved drug delivery systems.”
The research team compared the impact of standard urban particulate matter, mixed carbon nanoparticles, “bucky balls,” single-wall carbon nanotubes, and multiple wall carbon nanotubes on platelet clumping in humans and thrombosis in rats.
In both experiments, the mixed carbon nanoparticles had the most impact, provoking the greatest degree of platelet aggregation and the most dramatic reduction of carotid blood flow in the rats. The singlewall carbon nanotubes ranked second, the multiple wall nanotubes third and the standard urban particulate matter fourth in both experiments.
Bucky balls had virtually no effect. This gives the spherical, less adhesive bucky balls a potential advantage in the design of nanopharmaceutical devices for targeted drug delivery or imaging systems, the researchers note.
The impact of mixed carbon nanotubes and standard urban particulates suggests a risk of thrombosis from airborne pollution, in addition to the risk of atherosclerosis and heart attack.
First author of the paper is Anna Radomski, M.D., research associate at the IMM. Other UT Health Science Center co-authors include Paul Jurasz, Ph.D., and David Alonso-Escolano, Ph.D., both postdoctoral fellows at the IMM, and Maria Morandi, Ph.D., assistant professor of environmental and occupational health at the UT School of Public Health.
Co-authors from Ohio University are Tadeusz Malinski, Ph.D., the Marvin & Ann Dilley White Professor of Nanomedicine, and Magdalena Drews, M.D., postdoctoral fellow at the Department of Biochemistry. Radomski and Malinski are longstanding research collaborators, and Malinski developed the rat model of thrombosis employed in the study.
By Scott Merville, Public Affairs