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

Abstract

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.

Gold Nanoparticles in Diagnostics and Therapeutics for Human Cancer

“…On repeating the assay in the absence of E. coli , the authors observed a reduced toxicity effect, illustrating unforeseen artifacts that could occur in such widely used toxicity assays. Ginzburg et al showed a synergistic toxicity effect induced by gold nanoparticles in the presence of additives such as surfactants, while the individual components separately exhibited low toxicity [ 80 ], underlining the importance of identifying strategies for selecting safe nanoparticles-additive/ligand/modifier combinations. Gold nanoparticles were also shown to have species-specific differences with respect to biodistribution, pathophysiologic response, and retention time.…”

The Crucial Role of Environmental Coronas in Determining the Biological Effects of Engineered Nanomaterials

“…[172] For instance, surfactants (i.e., polysorbate 20, polysorbate 80, and SDS) exhibited synergistic toxicity with Au NPs in embryonic D. rerio, probably due to the increased bioavailability of surfactants by transport and internalization of the Au NPs. [173] Similarly, GO NSs coated with biological secretions in D. rerio culture water (e.g., small organic molecules, proteins, nucleotides, and mucopolysaccharides), induced more serious embryotoxicity in D. rerio with higher proportions of mortality and malformation. [97] In addition, tail flexure, pericardial edema, and faster heartbeat were observed in GO NS-treated juvenile fish.…”

Zebrafish as a Model to Evaluate Nanoparticle Toxicity

“…Other research with peptide-capped Au NPs showed that the terminal modification was important, with the presence of terminal histidines being more toxic than tryptophans, with methionine conferring the least toxicity [ 92 ]. In addition, co-incubation of zebrafish embryos with Au NPs and a surfactant (polysorbate 20) resulted in increased uptake and toxicity [ 93 ]. Together this suggests that the overall shape and surface chemistry of the Au NPs are key determinants of biocompatibility.…”