The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties

<div><p>Complex engineered nanomaterials (CENs) are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO₂ and hollow and non-hollow core-shell Ni@SiO₂ materials (i.e., ~1–2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively). Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations) and physiological (larval motility) endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution) to determine how toxicity differed between these CENs and equivalent quantities of Ni²⁺ salt (based on total Ni). Exposure to Ni²⁺ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO₂ and hollow Ni@SiO₂ provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO₂ showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO₂ and hollow Ni@SiO₂ material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to consider modification of the effective exposure when comparing different nanomaterial configurations, because effective exposure might influence NP toxicity more than specific “nano-chemistry” effects.</p>