Using living human cells, investigators at Pacific Northwest National Laboratory in Richland, Washington are devising new ways to test nanomaterials for safety. In the process, the model under consideration should reveal the information that will allow tracking of a pollutant from its entry point through a person’s organs, tissues, and cells and back to the environment:
“The process requires that live cells be grown on an infrared transparent substrate giving us an opportunity to closely examine the biological effects in living cells,” said Sundaram. Live cell Fourier transform infrared, FTIR, spectroscopy offers several attractive features for these investigations. These include the potential to detect biologically active nanoparticles without any prior knowledge of cell signaling pathways affected by them or need of a contrast agent to detect the biological response. Thus, live cell FTIR spectroscopy is expected to be a sentinel of exposure to help define nanoparticles that are biologically active, without bias of what that biological activity represents.
The PNNL scientists are also developing infrared transparent chemistries that are expected to improve FTIR measurements in live cell experiments. “We believe this is the first time FTIR spectroscopy has been used to examine the biological response of living cells to nanoparticles, and expect this technology will enable us to identify chemical changes associated with the biological response,” said Weber. FTIR spectroscopy measures a broad spectrum of chemical bonds and will provide information that is complementary to genomic and proteomic approaches.
FTIR spectra are captured in minutes in live cell studies, offering a tool for quick discovery of biomarkers of exposure that can determine whether nanoparticles are biologically active. This information can be used to prioritize nanoparticles for further study to ascertain the nature of the biological activity in terms of toxicity.
A broader approach to discovering what environmental nanomaterials can do once they enter the body – and how they enter and where they go – is being led by PNNL. This research is part of a $10 million, 5-year National Institutes of Health project designed to devise 3-D imaging and computational models that provide unsurpassed detail of respiratory systems in humans and other mammals.
Advancements in medical imaging, data analysis and computation have increased “the speed and accuracy of developing detailed models of the complete respiratory system,” reported Richard Corley, PNNL staff scientist and director of the multi-institutional study. “New imaging techniques also show promise for validating particle deposition models. Atlases of airway geometries and functional characteristics are also being constructed that will facilitate analyses of variability, reduce uncertainties in animal to human extrapolations and contribute to a more quantitative representation of environment-disease interactions.”