(87b) Development of in-Vivo Screening Benchmark for Complex Engineered Silica Nanoparticles

Silica nanomaterials have emerged as facile, easily modifiable templates for a wide range of applications, including biomedical imaging, drug delivery, catalysis, separations, and sensors.  More broadly, new applications of many types of functional nanomaterials has led to the development of engineered nanomaterials at an ever accelerating pace, and to a rapid increase in their use in consumer products, including cosmetics, sporting goods, clothing, and consumer electronics.  Concurrently, increasing evidence is indicating elevated toxicity of some nanomaterials, suggesting an urgent need to establish appropriate toxicity tests and thresholds for this emerging technology. 

Studies to-date have mostly concentrated on air contamination as the exposure route.  However, increasing use of nanomaterials-containing products is likely to result in an accumulation of these materials in the environment and hence increased risk from other exposure routes.  This motivates the need for the development of high-throughput screenings for nanomaterials toxicity along other exposure routes.  In our work, we are using a zebrafish (Dario rerio) model for toxicity screenings of complex nanomaterials in aqueous environments. Several factors make zebrafish excellent candidates for testing nanoparticle toxicity compared to more traditional in vivo models, including prolific breeding, embryo tissue transparency, rapid development time, and the simplicity of media-dosed toxin exposures.

In the present contribution, we are specifically investigating the possibility to utilize encapsulation of nanoparticles in nanostructured silica shells to simultaneously enhance material functionality and mitigate toxic effects.  We present results from a study in which the toxicity of carefully synthesized Ni-silica nanomaterials with different, well-controlled nanostructures is investigated.  Multi-component materials of this type, containing nanoparticles of one or more metal in combination with an inert matrix (here: silica), are expected to be especially important structures in emerging nanomaterial applications which widely rely on the use of embedded (rather than free) nanoparticles. 

The toxicity of surface-deposited Ni nanoparticles is compared to that of embedded and encapsulated metal nanoparticles.  Since porous silica nano- and microparticles have been shown to be non-toxic, it was hypothesized that embedding or encapsulation with this inert support could reduce or entirely mitigate nanoparticle toxicity while preserving the accessibility of the metal nanoparticle surface.  Our results demonstrate that porous silica coatings can indeed significantly lower the toxicity of metal nanoparticles compared to the equivalent dosing of analogous metal salts.  The toxicity trends can be explained by the high stability of the nanoparticles as indicated by a limited dissolution of metal ions from the structured materials into the media.  However, measurement of metal uptake into zebrafish tissues also indicates that particle transport and hence exposure can be increased as a result of silica structuring, suggesting the presence of a “Trojan horse”-like mechanism.  Thus, while nanostructuring can be useful for mitigating the toxicity of nanoparticles, it may also enable an entirely new mechanism of toxicity.