Synergistic Toxicity Produced by Mixtures of Biocompatible Gold Nanoparticles and Widely Used Surfactants

Nanoparticle safety is usually determined using solutions of individual particles that are free of additives. However, the size-dependent properties of nanoparticles can be readily altered through interactions with other components in a mixture. In applications, nanoparticles are commonly combined with surfactants or other additives to increase dispersion or to enhance product performance. Surfactants might also influence the biological activity of nanoparticles; however, little is known about such effects. We investigated the influence of surfactants on nanoparticle biocompatibility by studying mixtures of ligand-stabilized gold nanoparticles and Polysorbate 20 in embryonic zebrafish. These mixtures produced synergistic toxicity at concentrations where the individual components were benign. We examined the structural basis for this synergy using solution-phase analytical techniques. Spectroscopic and X-ray scattering studies suggest that the Polysorbate 20 does not affect the nanoparticle core structure. DOSY NMR showed that the hydrodynamic size of the nanoparticles increased, suggesting that Polysorbate 20 assembles on the nanoparticle surfaces. Mass spectrometry showed that these assemblies have both increased uptake and increased toxicity in zebrafish, as compared to the gold nanoparticles alone. We probed the generality of this synergy by performing toxicity assays with two other common surfactants, Polysorbate 80 and sodium dodecyl sulfate. These surfactants also caused synergistic toxicity, although the extent and time frame of the response depends upon the surfactant structure. These results demonstrate a need for additional, foundational studies to understand the effects of surfactants on nanoparticle biocompatibility and challenge traditional models of nanoparticle safety where the matrix is assumed to have only additive effects on nanoparticle toxicity.