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CHAPEL HILL - Bacteria mutate for a living, evading antibiotic drugs while killing tens of thousands of people in the United States each year. But as concern about drug-resistant bacteria grows, one novel approach under way at the University of North Carolina at Chapel Hill seeks to thwart the bug without a drug by taking a cue from nature.
Mark Schoenfisch and his lab of analytical chemists at UNC have created nano-scale scaffolds made of silica and loaded with nitric oxide (NO) - an important molecule in mammals that plays a role in regulating blood pressure, neurotransmission and fighting bacterial infections, among other vital functions.
"There was evidence that nitric oxide kills bacteria, but the difficult part involved storing it in a manner such that it could be delivered to bacterial cells," said Evan Hetrick, a doctoral student in Schoenfisch's lab and lead author on a paper in the February issue of the American Chemical Society's journal ACS Nano.
While the body constantly produces NO, and can ramp up its production to fight infection, sometimes it can't produce enough to mount a sufficient defense. Previous research using small molecules to deliver NO hit roadblocks - controlling the release of the compound was difficult and the molecules were potentially toxic to healthy cells in the body.
"With silica scaffolds, nitric oxide stores easily and we could very carefully control the release," said Schoenfisch, an associate professor of chemistry in UNC's College of Arts and Sciences.
Schoenfisch, Hetrick and their colleagues tested their silica scaffolds head-to-head with small molecules against the bacteria Pseudomonas aeruginosa, which is commonly found in burn and other wound infections.
NO delivered by both methods completely killed the bacteria. But the silica nanoparticles delivered the NO right to the bacteria's doorstep. In contrast, the small molecules released NO indiscriminately, and the concentration of NO is lost as it makes its way toward bacterial cells.
"With the silica particles, more NO actually reached the inside of the cells, enhancing the efficacy of the nanoparticles compared to the small molecule. So, the overall amount of NO needed to kill bacteria is much less with silica nanoparticles," Schoenfisch said. "And, with small molecules, you're left with potentially toxic byproducts," Schoenfisch said. Using mouse cells, they proved that the silica nanoparticles weren't toxic to healthy cells, but the small molecules were.
Schoenfisch has a history of success with NO-releasing materials. His lab has successfully created a variety of coatings for different biomedical applications. Such materials hold promise as anti-infective coatings and as methods to improve the body's integration of biological implants - such as hip or knee joints - and implanted sensors that relay various biological measures, such as blood glucose or oxygen concentrations.
The amount and rate of NO release are easily modified and controlled by using these different silica nanoparticles. "Release rates are a function of the precursors used to make the nanoparticles," Schoenfisch said. "It depends entirely on how we build the silica structures."
Future research will include studying additional bacterial strains, active targeting, preferential uptake and biodistribution studies.
University of North Carolina at Chapel Hill. February 2008.
November 19, 2008 -- Researchers in New Mexico and Florida are reporting development of microscopic particles that act as chemical booby traps for bacteria. The traps attract and kill up to 95 percent of nearby bacteria, including microbes responsible for worrisome hospital-based infections. The scientists describe their discovery as micro-sized “roach motels” for harmful bacteria. Their study is scheduled to go online November 24 in the premiere issue of ACS Applied Materials & Interfaces, a new monthly journal. It is scheduled for the January 28 print edition.
In the report, David G. Whitten of the University of New Mexico and Kirk S. Schanze of the University of Florida, working together with a team of faculty and graduate student collaborators, point out that bacterial contamination of medical devices causes up to 1.4 million deaths per year. In addition, bacteria are becoming more resistant to standard disinfection methods. Scientists also are increasingly concerned about the possibility of intentional release of harmful bacteria by terrorists. As a result, researchers are attempting to develop new and improved methods of disinfection.
The New Mexico and Florida groups describe an advance toward this goal. It involves the development of light-activated, hollow microcapsules composed of an organic conducting polymer. The antibacterial microcapsules can attract, capture, and kill bacteria. In controlled laboratory tests, the researchers exposed the capsules to either Pseudomonas aeruginosa, one of the deadliest and most common hospital-based pathogens, or Cobetia marina, a type of bacterium that fouls the hulls of ships and other marine equipment. After one hour of light exposure, the light-activated capsules killed more than 95 percent of the exposed bacteria, the researchers say. The microcapsules can be applied to a variety of surfaces, including medical equipment, they add.
News release courtesy of The American Chemical Society, a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences.