(527d) Structure-Toxicity Correlations for Ni/SiO2 Complex Engineered Nanomaterials Using High-Throughput Zebrafish Assays

Functional nanomaterials are developing at an ever accelerating pace and are finding application in a wide range of industrial and consumer products despite evidence that nanomaterials can show elevated toxicity.  Furthermore, while bare nanoparticles (NPs) are rarely used in industrial application due to sintering and deactivation effects, embedded NPs (so-called complex engineered nanomaterials, CEN) have found little attention in nanotoxicological studies to-date. This motivates a need for the development of rapid, yet sensitive, high throughput in vivo nanotoxicity screening assays. 

    We are investigating three differently structured Ni/SiO₂ nanomaterials as model CEN with the aim to evaluate different nanotoxicity assays and develop structure-toxicity correlations for CEN that will allow derivation of predictive toxicity models. The CEN are comprised of Ni NPs embedded in or on (non-toxic) porous silica NPs, based on the hypothesis that embedding nickel nanoparticles in silica could reduce or entirely mitigate nanotoxicity while still providing accessibility and hence maintaining functionality of the embedded NP. The three CEN structures are nickel NPs (a) embedded in hollow porous silica shells (hNi@SiO₂), (b) encapsulated in non-hollow, porous silica NPs (nhNi@SiO₂), and (c) deposited on the silica nanoparticle’s external surface (Ni-SiO₂).  All CENs were thoroughly characterized via TEM, XRD, BET, as well as for dissolution, aggregation, and settling properties, followed by multiple 5-day zebrafish developmental toxicity assays including survival, malformation, hatching, and motility. Zebrafish (Danio rerio) were used as a well-suited toxicity model due to prolific breeding and rapid development time. The toxicity results were then correlated with the CEN properties to determine structure-toxicity correlations. 

    All three nanomaterials mitigated toxicity compared to the respective Ni²⁺ dose and showed high zebrafish survival.  Zebrafish motility, which probes persistent neurotoxicity, emerged as a more sensitive assays and revealed lowest toxicity for nhNi@SiO₂, explained by lower nickel dissolution compared to the other two nanomaterials.  In contrast, this material showed the highest toxicity of the three CENs in hatching assays, which can be traced back to resistance to aggregation which facilitates uptake through the chorion.  Overall, the toxicity results are consistent with a ‘Trojan horse’ mechanism and point towards complexity and pitfalls when establishing structure-toxicity correlations and the necessity of combining multiple assays to fully assess nanomaterials toxicity.