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Nanobiotech innovations move forward at U.S., U.K. research institutes


By David Schwartz
Published: March 17th, 2010

Chemical engineers at the Massachusetts Institute of Technology (MIT) have built a sensor array that can detect single molecules of hydrogen peroxide emanating from a single living cell. Hydrogen peroxide has long been known to damage cells and their DNA, but scientists have recently uncovered evidence that points to a more beneficial role: it appears to act as a signaling molecule in a critical cell pathway that stimulates growth, among other functions. When that pathway goes awry, cells can become cancerous, so understanding hydrogen peroxide’s role could lead to new targets for potential cancer drugs, says Michael Strano, PhD, MIT’s Charles and Hilda Roddey associate professor of chemical engineering, who led the research team. Strano and colleagues describe the sensor array, which is made of carbon nanotubes, in Nature Nanotechnology.

The researchers used the array to study the flux of hydrogen peroxide that occurs when a common growth factor called EGF activates its target, a receptor known as EGFR, located on cell surfaces. The team showed that hydrogen peroxide levels more than double when EGFR is activated. EGF and other growth factors induce cells to grow or divide through a complex cascade of reactions inside the cell. It’s still unclear exactly how hydrogen peroxide affects this process, but Strano speculates that it may somehow amplify the EGFR signal, reinforcing the message to the cell. Because hydrogen peroxide is a small molecule that doesn’t diffuse far (about 200 nanometers), the signal would be limited to the cell where it was produced. The team also found that in skin cancer cells, believed to have overactive EGFR activity, the hydrogen peroxide flux was 10 times greater than in normal cells. Because of that dramatic difference, Strano believes this technology could be useful in building diagnostic devices for some types of cancer. “You could envision a small handheld device, for example, which your doctor could point at some tissue in a minimally invasive manner and tell if this pathway is corrupted,” he says.

Researchers in Strano’s lab plan to study different forms of the EGF receptor to better characterize the hydrogen peroxide flux and its role in cell signaling. Strano’s team also is working on carbon nanotube sensors for other molecules. The team already has successfully tested sensors for nitric oxide and ATP — the molecule that carries energy within a cell. “The list of biomolecules that we can now detect very specifically and selectively is growing rapidly,” says Strano, who adds that the ability to detect and count single molecules sets carbon nanotubes apart from many other nanosensor platforms.

Across the pond, scientists at the John Innes Centre (JIC) of the U.K.’s Biotechnology and Biological Sciences Research Council (BBSRC) have succeeded in growing empty particles derived from a plant virus and in prompting them to carry useful chemicals. The containers are particles of the Cowpea mosaic virus, which is ideally suited for designing biomaterial at the nanoscale. The external surface of these nano containers could be decorated with molecules that guide them to where they are needed in the body before the chemical load is discharged to exert its effect on diseased cells. “This is a shot in the arm for all Cowpea mosaic virus technology,” says George Lomonossoff, PhD, professor of biological chemistry at the JIC and co-author of a paper describing the technology in Small.

Scientists have tried to empty virus particles of their genetic material using irradiation or chemical treatment. Though successful in rendering the particles non-infectious, these methods have not fully emptied the particles. The JIC scientists discovered they could assemble empty particles from precursors in plants and then extract them to insert chemicals of interest. Previously, scientists at JIC and elsewhere had managed to decorate the surface of virus particles with useful molecules, “but now we can load them, too, creating fancy chemical containers” — an innovation that opens up new areas of research, says lead author Dave Evans, PhD, in the department of biological chemistry.

One application could be in cancer treatment. Integrins are molecules that appear on cancer cells. The virus particles could be coated externally with peptides that bind to integrins. This would mean the particles seek out cancer cells to the exclusion of healthy cells. Once bound to the cancer cell, the virus particle would release an anti-cancer agent that has been carried as an internal cargo. “The potential for developing Cowpea mosaic virus as a targeted delivery agent of therapeutics is now a reality,” Evans says. Patents have been filed on the empty viral particles, their use, and the processes by which they are made. The IP management company Plant Bioscience Limited, which handles most of the JIC’s tech transfer activity, is managing the technology’s commercialization.

Source: Science Daily and EurekAlert!

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