Internalization and Fate of Engineered Nanomaterials in Developing Zebrafish Embryos
EMSL Project ID
44625
Abstract
The growing commerce in micro- and nanotechnology is expected to increase human exposure to submicrometer and nanoscale particles. 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 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, yet strongly susceptible to environmental insults. These studies will directly contribute to EMSL mission in supporting environmental molecular research, and target EMSL Science of Interfacial Phenomena Science Theme by investigating the interactions of nanoparticles with biological 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 unique properties of nanomaterials, such as their large surface area to mass ratio, which increase their reactivity. Our studies will therefore be focused on individual particles or nanoscale aggregates, guided by the working hypothesis that the surface properties of the individual nanoparticle dictate the internalization pathways and fate, and ultimately govern the 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 fluorescence sensitivity and spatial (nm) resolution. We will take advantage of EMSL's unique capabilities in high sensitivity fluorescence imaging to identify and track fluorescent nanoparticles with well defined surface properties. We will also use EMSL's new multi-photon confocal fluorescence microscope to gain deep tissue penetration of the laser excitation light with minimal tissue damage to investigate live embryos as they develop over 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
2011-10-01
End Date
2012-09-30
Status
Closed
Released Data Link
Team
Principal Investigator