Pathways and fate of individual nanoparticles in vivo; a whole organism approach
EMSL Project ID
30426
Abstract
The growing commerce in micro- and nanotechnology is expected to increase human exposure to submicrometer and nanoscale particles, including certain forms of amorphous silica nanoparticles. Adverse effects of these 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 organelles or organs, but the internalization pathways and fate of the particles, which determine the response of the organism and the impact on its function, are still unclear. Furthermore, the role of particle surface properties in these processes and the consequent impact on the health of the organism is largely unknown. Here we propose to investigate the internalization pathways, interactions and fate of individual fluorescent nanoparticles with well defined surface properties, and correlate these processes with the response and survival of the organism. By focusing on zebrafish embryos, these studies will identify nanoparticle properties that govern particle toxicity or biocompatibility during development, when biological processes are highly conserved among species, and are most essential yet strongly susceptible to chemical insults. These studies will 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. Although large aggregates of nanoparticles have been found within cells and organisms, it is thought that such agglomeration occurs as the result of experimental conditions where the local concentration is high. It is currently thought that large agglomerates can be easily detected by macrophages, but individual nanoparticles or small aggregates (<100 nm) can escape this defense mechanism and directly enter the circulatory system through the epithelial walls. Our studies will therefore be guided by the working hypothesis that the interaction of living systems with nanomaterials in vivo occurs under conditions where nanomaterials are kept as individual particles or nanoscale aggregates, and that the surface properties of the individual nanoparticle dictate its internaliation pathways and fate, and ultimately govern its level of toxicity. The investigation of dynamic interactions and pathways of individual or small clusters of nanoparticles requires tools that gain insights into living systems with high spatial (nm) and temporal (ms) resolutions. We will take advantage of EMSLs unique capabilities in high sensitivity fluorescence imaging to identify and track individual fluorescent nanoparticles with well defined surface properties. Using time-lapse multi-channel fluorescence imaging, combined with DIC microscopy, it will be possible to follow individual nanoparticles and delineate their interactions, pathways and fate within zebrafish embryos in real time. By correlating the interactions and fate of the particles with the response and survival of the organism it will be possible to understand the mechanisms that underlie nanoparticle potential toxicity and delineate desired surface properties for designing safer nanomaterials and exposure guidelines.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-09-04
End Date
2011-09-30
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.