External Cell/Tissue Dose (Delivery)
PNNL researchers have developed core capabilities in engineered nanomaterial generation and animal exposure and are using these to identify biosignatures of respiratory effects induced by nanomaterial exposure.
While biomarkers of exposure and response have been developed for some environmental pollutants, they have not been developed for engineered nanomaterials, and furthermore, biomarkers in tissues, such as blood, which require invasive sampling techniques, have been the typical targets. Biomarkers with strong linkages to the underlying disease process are needed to advance the field of biomarker discovery for environmental respiratory tract diseases linked to nanomaterial exposure.
Dose for nanoparticles in vitro increases in specificity and relevancy as dose measures move from administered amount to amount delivered to cells or internalized by cells. Enlarged View
PNNL has developed core capabilities in engineered nanomaterial generation and animal exposure, and uses these capabilities to: 1) generate respiratory tract tissue and fluid samples suitable for "omics"-driven biosignature discovery; 2) conduct a combination of proteomic and biochemical (tumor necrosis factor-alpha [TNF-a], malo-ndialdehyde) analyses on bronchio-alveolar and nasal lavage fluids as well as exhaled breath condensate; and 3) identify biosignatures of nanoparticulate matter-induced respiratory effects from these data. In addition, PNNL has developed a corresponding high-throughput in-vitro system for identifying biosignatures of epithelial cell and macrophage response to engineered nanomaterial.
We are identifying biosignatures of respiratory effects induced by these nanomaterials that are testable in humans and generate important mechanistic data that can be used to more fully realize the predictive value of an available virtual respiratory tract (VRT) model.
Publication:
Teeguarden JG, PM Hinderliter, G Orr, BD Thrall, and JG Pounds. 2007. "Particokinetics In Vitro: Dosimetry Considerations for In-Vitro Nanoparticle Toxicity Assessments." Toxicological Sciences 95(2):300-312. Details .
Contact: Justin Teeguarden