Surface functionalisation-dependent adverse effects of metal nanoparticles and nanoplastics in zebrafish embryos

The growing number of manufactured nanomaterials (MNMs) used in consumer products and industrial applications is leading to increased exposures whose consequences are not yet fully understood in terms of potential impacts on human and ecosystem health. Thus, there is an urgent need to further develop high throughput testing for hazard prediction in nanotoxicology. The zebrafish (Danio rerio) embryo has emerged as a vertebrate model organism for nanotoxicity studies, as it provides superior characteristics for microscopy-based screening and can describe the complex interactions of MNMs with a living organism. Automated microscopy coupled with image acquisition has facilitated hazard assessment of chemicals by quantification of various endpoints (e.g., mortality, malformations, hatching), an approach which we employed here to address adverse effects of a selected library of MNMs of different compositions and surface functionalities. We investigated metal and metal oxide MNMs with mean primary particle sizes of 5 to 50 nm, different chemical compositions (silica, ceria, titania, zinc oxide and silver) and various surface coatings / functionalisation, including OECD reference materials. In addition, we tested as proxies representatives for of nanoplastics polystyrene and polymethylmethacrylate nanoparticles which were surface modified by either amino- or carboxyl-groups. Our systematic analysis to establish quantitative property-activity relationships revealed a pronounced toxicity of silver and amino-modified polystyrene nanoparticles (NPs), evidenced by reduced survival and malformations. Interference with hatching, however, was the most sensitive endpoint, as zinc oxide as well as silver NPs reduced hatching already at lower concentrations (i.e., 0.5 and 1 µg/mL, respectively) and early time points (3 days post fertilization, dpf). Interestingly, carboxylated polystyrene NPs and carboxylated or amino-modified polymethylmethacrylate NPs were non-toxic, highlighting both surface modification and core chemistry of nanoplastics as key determinants of biocompatibility.