(540c) Development of in-Vivo Toxicity Screening Benchmarks for Complex Engineered Nanomaterials

Functional nanomaterials are developing at an ever accelerating pace and are already finding widespread application in consumer products including cosmetics, sporting goods, clothing, and consumer electronics.  However, increasing evidence indicates that nanomaterials are showing elevated toxicity, motivating the need to establish appropriate toxicity tests for these emerging technology.  Silica nanomaterials have been identified for a wide range of applications including biomedical imaging, drug delivery, catalysis, separations, and sensors, as they constitute a versatile, easily modifiable template that has been established as being non-toxic.  However, the rapidly increasing volume of nanomaterials research and production requires development of modern high-throughput in vivo nanotoxicity screenings for these nanomaterials.  Zebrafish (Danio rerio) is rapidly emerging as a well-suited model for such studies due to prolific breeding, embryo tissue transparency, rapid development time, and the relative simplicity of controlled toxin exposure. 

    Porous silica nano- and microparticles are accepted to be non-toxic, thus leading to the hypothesis that embedding metal nanoparticles in silica could reduce or entirely mitigate nanoparticle toxicity while still providing accessibility of the metal nanoparticle surface and hence maintaining the functionality of the embedded nanoparticle.  Three different complex nanostructures are investigated in this work including surface-deposited metal nanoparticles on silica nanoparticle supports, embedded metal nanoparticles in silica and encapsulated metal nanoparticles in silica.  In the present work, the toxicity of carefully synthesized Ni-silica nanomaterials with these complex, but well-controlled nanostructures is investigated using zebrafish as the in vivo toxicity model.

    Comparing the different structures, our results from the in vivo zebrafish toxicity study demonstrate that all three silica configurations significantly reduce the toxicity of metal nanoparticles compared to the equivalent dosing of an analogous metal salt.  While the engineered nanomaterials showed limited dissolution of metal ions from the structured materials into the media solution, nickel uptake was still detectable at ng levels within the zebrafish larvae tissue.  Interestingly, relative to free metal ion concentrations, metal uptake was significantly enhanced for the engineered nanomaterials, suggesting the presence of a “trojan horse” transport mechanism into the fish.  All three engineered nanomaterials showed high zebrafish survival rates as compared to the Ni salts, hence necessitating more sensitive means for detection of possible toxic effects.  Therefore, the studies were extended to include motility analysis which allowed for a much enhanced sensitivity compared to endpoints of survival and developmental deformations, yielding  statistically significant dose-dependent results for the different nanomaterials.  Our current work includes extension of these studies to a range of nanoparticle sizes and metals to further investigate the effect of nanostructuring on nanomaterial toxicity.