Functional silver-based nanomaterials affecting zebrafish development: the adverse outcomes in relation to the nanoparticle physical and chemical structure

The growing demand for effective antimicrobials determined a significant increase of new nanoformulated materials to fight against bacteria and viruses, to be used in many industrial sectors including textiles, cosmetics, pharmaceuticals, and air and water filtering. Nano silver (Ag)-based materials, well-known for their antibacterial properties, are among the most exploited ones. However, the toxicity mechanisms of Ag nanoparticles (NPs) are still debated, requiring more evidence to support a safe-by-design (SbD) strategy for these materials. This study used zebrafish (D. rerio) to assess and compare the toxic and adverse effects (AEs) of commercial Ag-NPs (naked and PVP-coated) and newly synthesized hydroxyethylcellulose-coated Ag-NPs in solution (Ag-HECs) or the powder (Ag-HECp) form. Statistical correlation analysis between AEs and NP physico-chemical (p-chem) properties, such as size, surface charge, and solubility, was also performed. The results ranked the materials as follows in terms of acute lethality (LC50) and malformation (EC50) effects: Ag-HECp > Ag-HECs > Ag-PVP > Ag-NKD. Notable AEs included axial defects, pericardial edema, and reduced lipid yolk consumption, impacting embryo growth and hatching time. Correlation analyses showed that the stabilizing agent HEC, though a safe polymer, played a significant role in modulating Ag-NPs' reactivity toward embryonic structures. The study discusses the biological mode of action and potential molecular events underlying the observed effects. These findings contribute to understanding the biological targets and AEs modulated by tuning Ag-NPs' properties and will additionally feed the SbD frameworks under development for implementing safe and sustainable Ag-based nano-enabled antimicrobial materials.