HOUSTON – (Oct.
21, 2005) --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 report in an upcoming
edition of the British Journal of Pharmacology.
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
"We found that some carbon nanoparticles activate
human platelets and stimulate them to aggregate,
or clump together. We also demonstrate 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 (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 could also enhance
"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."
In a paper posted online last month ahead of publication,
the team compared the impact of standard urban particulate
matter, mixed carbon nanoparticles, "bucky balls," single-wall
carbon nanotubes, and multiple wall carbon nanotubes
on human platelet clumping 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 single-wall
carbon nanotubes ranked second, the multiple wall
nanotubes third and the standard urban particulate
matter fourth in both experiments.
These four types of nanoparticles also were shown
to activate a receptor on platelets that is vital
to their aggregation – the glycoprotein integrin
receptor. This seems to be the underlying mechanism
for the nanoparticle's effects, the researchers note,
but each nanoparticle employed a different molecular
pathway to activate the receptor.
Bucky balls had virtually no effect. Nanotubes appear
to mimic molecular bridges involved in platelet interactions
while the bucky balls do not. 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
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 post-doctoral
fellows at the IMM, and Maria Morandi, Ph.D., assistant
professor of environmental and occupational health
at the UT School of Public Health at Houston.
Co-authors from Ohio University are Tadeusz Malinski,
Ph.D., Marvin & Ann Dilley White Professor of
Nanomedicine, and Magdalena Drews, M.D., post-doctoral
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.