Compiled by BioPhotonics staff
STANFORD, Calif. – In a mouse study, engineered nanoparticles have been proved safe when administered by two alternative routes, marking the first step up the ladder of toxicology studies. Within a year and a half, they could be used in human trials for detection of colorectal and, possibly, other cancers.
The particles measure 100 nm in diameter and have special optical properties in the materials surrounding the gold centers. Although light typically bounces off a material’s surface at the same wavelength at which it hits it, in these specialized materials, about one ten-millionth of the incoming light bounces back in a pattern of discrete wavelengths characteristic of that material. Molecules that home in on cancer cells can be affixed to them.
Until now, there was no proof that the particles were not toxic. Researchers at Stanford University School of Medicine – who developed some nanoparticles in collaboration with Oxonica Materials, a small company owned by Boston-based Cabot Corp. – administered them into two groups of mice to disprove any threats of toxicity. In each case, the dose was 1000 times as large as would be required to get a clear signal from the nanoparticles.
In the first group of mice, the scientists administered the nanoparticles rectally. They followed up with a series of measurements at five time points, ranging from 5 minutes to two weeks. The group monitored each test animal’s blood pressure, electrocardiograms and white-blood-cell counts, and they examined several tissues for signs of physiological stress on their cells. They also stained tissues with dyes that flag dying cells.
All tests to assess the toxicity of the nanoparticles yielded virtually no signs of stress to any tissues, and none at all two weeks after administration. Most importantly, the scientists inspected tissues via electron microscopy to see where the gold-containing particles were lodged and could not find any gold present outside the bowel.
The researchers’ conclusion was that, because the nanoparticles remained confined to the organ when rectally administered, they posed no threat of systemic toxicity.
The nanoparticles were administered intravenously to the second group of 60 mice, and scant signs of inflammation or other evidence of toxicity were found. Virtually no signs were present after two weeks.
The findings, which appeared in the April 20, 2011, issue of Science Translational Medicine (doi: 10.1126/scitranslmed. 3001963), have opened the door to testing humans with intravenous injections of the nanoparticles to search for tumors throughout the body. The team has filed for FDA approval to proceed with clinical studies of nanoparticle administration for the diagnosis of colorectal cancer.