Tissue distribution and fate of nanoparticles following in vivo exposure
EMSL Project ID
30427
Abstract
The growing commerce in micro- and nanotechnology is expected to increase human exposure to submicrometer and nanoscale engineered particles. Adverse effects of submicrometer and nanoscale particles on living systems have been demonstrated, but the underlying mechanism is far from being understood. Nanoparticles can enter an organism through multiple pathways and accumulate within multiple organs and tissues, but the distribution and fate of the particles, which determine the response of the organism and the impact on its health, are still unclear. Furthermore, the role of particle size in these processes and the consequent impact on the health of the organism is largely unknown. Here we propose to investigate the tissue distribution and fate of fluorescent nanoparticles with different sizes following single parenteral or lung exposures of F344 female rats. By screening multiple organs and tissues at different time points after exposure, it will be possible to determine the size-dependent distribution of the nanoparticles and their fate within the organism. This information will aid in establishing exposure guidelines and designing biocompatible nanoparticles. These studies will therefore directly contribute to EMSL mission in supporting environmental research, and target EMSL Biological Interactions and Dynamics Science Theme by focusing on the Impact of Nanotechnology on Living Systems. Accumulating observations suggest that nanoscale particles exert harmful effects on living systems to a greater extent than larger particles, and these effects have been linked to the surface properties of nanomaterial. It has been also thought that larger particles can be easily detected by macrophages, but nanoparticles might be able to escape this defense mechanism and enter the circulatory system through the epithelial or endothelial walls, reaching remote tissues and organs from the entry site. Our studies will therefore be guided by the working hypothesis that the size of the particle determines its tissue distribution and fate within the organism and that nanoparticles are likely to be distributed at remote locations from the site of exposure. We will use fluorescent polystyrene particles tagged with a fluorescent dye that is excited and emits at the far red wavelengths to minimize signal from tissue autofluorescence. We are uncertain whether particles will be distributed diffusely across organs and tissues, where single particles might be present within a field of view, or whether particles will be present as aggregates. Therefore, we will take advantage of EMSLs unique capabilities in high sensitivity fluorescence imaging at the far red wavelengths to screen tissue sections taken at different time intervals post exposure. Using multichannel fluorescence imaging, and fluorescent or non-fluorescent dyes and probes specific for distinct cell populations or organelles, it will be possible to determine the target of the particles (singlets or aggregates) and their fate within the organism, organ or cell. By identifying the in vivo distribution and fate of particles with different sizes, following two distinct exposure pathways, it will be possible to delineate size-dependent potential toxicity or biocompatibility and aid in formulating preventative approaches. In addition, these data will be applied to development of a physiologically based pharmacokinetic model for nanoparticles.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-09-24
End Date
2009-12-10
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
6 Orr G, Panther DJ, Cassens KJ, Phillips JL, Tarasevich BJ, Pounds JG. Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane. Toxicology and Applied Pharmacology. 2009, 236, 210-220.
6 Orr G, Panther DJ, Cassens KJ, Phillips JL, Tarasevich BJ, Pounds JG. Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane. Toxicology and Applied Pharmacology. 2009, 236, 210?220.