Silver nanoparticle toxicity in the embryonic zebrafish is governed by particle dispersion and ionic environment

Abstract

The mechanism of action of silver nanoparticles (AgNPs) is unclear due to the particles’ strong tendency to agglomerate. Preventing agglomeration could offer precise control of the physicochemical properties that drive biological response to AgNPs. In an attempt to control agglomeration, we exposed zebrafish embryos to AgNPs of 20 or 110 nm core size, and polypyrrolidone (PVP) or citrate surface coatings in media of varying ionic strength. AgNPs remained unagglomerated in 62.5 μM CaCl2 (CaCl2) and ultrapure water (UP), but not in standard zebrafish embryo medium (EM). Zebrafish embryos developed normally in the low ionic strength environments of CaCl2 and UP. Exposure of embryos to AgNPs suspended in UP and CaCl2 resulted in higher toxicity than suspensions in EM. 20 nm AgNPs were more toxic than 110 nm AgNPs, and the PVP coating was more toxic than the citrate coating at the same particle core size. The silver tissue burden correlated well with observed toxicity but only for those exposures where the AgNPs remained unagglomerated. Our results demonstrate that size- and surface coating-dependent toxicity is a result of AgNPs remaining unagglomerated, and thus a critical-design consideration for experiments to offer meaningful evaluations of AgNP toxicity.

Developing a Novel Embryo–Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

“…28 To minimize agglomeration with salts present in zebrafish embryo medium, the ZnO NP exposures were conducted in ultrapure water. 28,29 As previously reported in Wehmas et al, this ZnO NP has a mean hydrodynamic diameter on the order of microns when prepared in zebrafish embryo medium, whereas its mean hydrodynamic diameter is *400 nm and zeta potential (an indication of charge) is *20.2 mV when prepared in ultrapure water creating a more stable exposure suspension. 28 Following addition of compound, the 96-well plates were sealed with Parafilm, wrapped in aluminum foil to block incidental light and maintained in a 33°C -1°C incubator until 7 DPF.…”

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…Different types of superficial agents may generate coating-specific behavior of AgNPs in solution [66] or in physiological fluids [13], and consequently may cause different antimicrobial or toxic effects.…”

“…Among other effects, it was demonstrated that carbon-coated silver nanoparticles influence cell viability to a lesser extent than uncoated AgNPs of similar size [95], whereas polysaccharide-coated AgNPs cause more severe effects than uncoated AgNPs [1]. Moreover, it was shown that PVP-coated [66] or peptide-coated [51] AgNPs are more toxic than citrate-coated AgNPs with similar particle core sizes.…”

Decreased bacterial growth on titanium nanoscale topographies created by ion beam assisted evaporation

“…Silver is one of the most prominent non-small-molecule drugs used for antibacterial applications, 3,[17][18][19] but can be expensive and mildly toxic to surrounding mammalian cells. 20,21 Additionally, adding different materials to the surface may lead to imperfectly fused layers that may eventually wear or delaminate from the bulk implant.…”