Human Enzyme Found to Break Down Toxic Nanomaterials

PITTSBURGH, Pennsylvania, April 7, 2010 (ENS) – A human enzyme that can biodegrade carbon nanotubes and offset the damaging health effects of being exposed to these tiny components has been identified by an international team of researchers based at the University of Pittsburgh.

Carbon nanotubes are one-atom thick rolls of graphite 100,000 times smaller than a human hair yet stronger than steel.

They are used to reinforce plastics, ceramics or concrete; they are excellent conductors of electricity and heat and also are sensitive chemical sensors.

But a nanotube’s surface contains thousands of atoms that could react with the human body in unknown ways. Tests on mice have shown that nanotube inhalation results in severe lung inflammation coupled with scarring of the lungs known as fibrosis.

The durability of carbon nanotubes raises additional concerns about proper disposal and cleanup.

The research team reported today in the journal “Nature Nanotechnology” that their results could open the door to the use of carbon nanotubes as a safe drug-delivery tool. Their findings also could lead to the development of a natural treatment for people exposed to nanotubes, either in the environment or the workplace.

The researchers found that carbon nanotubes degraded with the human enzyme myeloperoxidase (hMPO) did not produce the lung inflammation that intact nanotubes have been shown to cause.

Dr. Valerian Kagan in his lab at the University of Pittsburgh (Photo courtesy U. Pitt)

They also found that the white blood cells which contain and emit hMPO to kill invading microorganisms can be directed to attack only carbon nanotubes.

“The successful medical application of carbon nanotubes rely on their effective breakdown in the body, but carbon nanotubes also are notoriously durable,” said lead researcher Valerian Kagan, a professor and vice chair in the Department of Environmental and Occupational Health in Pitt’s Graduate School of Public Health.

“The ability of hMPO to biodegrade carbon nanotubes reveals that this breakdown is part of a natural inflammatory response,” said Dr. Kagan. “The next step is to develop methods for stimulating that inflammatory response and reproducing the biodegradation process inside a living organism.”

Kagan and his research group led a team of more than 20 researchers from universities in Sweden, Ireland and the United States along with the laboratory groups of Alexander Star, an assistant professor of chemistry in Pitt’s School of Arts and Sciences, and Judith Klein-Seethharaman, an assistant professor of structural biology in Pitt’s School of Medicine.

In 2008, Star and Kagan reported in “Nano Letters” that carbon nanotubes deteriorate when exposed to the plant enzyme horseradish peroxidase, but their research focused on cleanup after accidental spills during manufacturing or in the environment.

For the current study, the researchers focused on human MPO because it works by releasing strong acids and oxidants similar to the chemicals used to break down carbon nanotubes.

They first incubated short, single-walled nanotubes in an hMPO and hydrogen peroxide solution for 24 hours, after which the structure and bulk of the nanotubes had completely degenerated.

The nanotubes degenerated even faster when common table salt, sodium chloride, was added to the solution to produce hypochlorite, a strong oxidizing compound known to break down nanotubes.

After establishing the effectiveness of hMPO in degrading carbon nanotubes, the team developed a technique to prompt the white blood cells to attack nanotubes by capturing them and exposing them to the enzyme.

They implanted a sample of nanotubes with antibodies known as immunoglobulin G (IgG), which made them specific targets for the white blood cells.

After 12 hours, 100 percent of the IgG nanotubes were degraded versus 30 percent of those without IgG.

In subsequent laboratory tests, lung tissue exposed to the degraded nanotubes for seven days showed little change when compared to unexposed lung tissue. But lung tissue exposed to untreated nanotubes developed severe inflammation.

Additional Pitt researchers included Yulia Tyurina, a Pitt assistant professor of environmental and occupational health in the Graduate School of Public Health, and Donna Stolz, an associate professor of cell biology and physiology in Pitt’s medical school.

Other participating researchers are from Sweden’s Karolinska Institute, Trinity College in Ireland, West Virginia University and the National Institute for Occupational Safety and Health.

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