Department of Chemistry and Biochemistry , University of Oregon , Eugene , Oregon 97403 , United States.
Department of Environmental and Molecular Toxicology and the Sinnhuber Aquatic Research Laboratory , Oregon State University , Corvallis , Oregon 97333 , United States.
ACS Nano. 2018 Jun 26;12(6):5312-5322. doi: 10.1021/acsnano.8b00036. Epub 2018 May 16.
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.
纳米颗粒的安全性通常是通过使用不含添加剂的单个颗粒溶液来确定的。然而，纳米颗粒的尺寸依赖性特性可以通过与混合物中的其他成分相互作用而轻易改变。在应用中，纳米颗粒通常与表面活性剂或其他添加剂结合使用，以增加分散度或增强产品性能。表面活性剂也可能影响纳米颗粒的生物活性；然而，人们对此知之甚少。我们通过研究配体稳定的金纳米颗粒与聚山梨酯 20 在胚胎斑马鱼中的混合物，研究了表面活性剂对纳米颗粒生物相容性的影响。这些混合物在各组分无害的浓度下产生协同毒性。我们使用溶液相分析技术研究了这种协同作用的结构基础。光谱和 X 射线散射研究表明，聚山梨酯 20 不影响纳米颗粒的核心结构。DOSY NMR 表明纳米颗粒的水动力尺寸增加，表明聚山梨酯 20 在纳米颗粒表面组装。质谱表明，与单独的金纳米颗粒相比，这些组装体在斑马鱼中的摄取量增加，毒性也增加。我们通过对另外两种常见表面活性剂聚山梨酯 80 和十二烷基硫酸钠进行毒性测定，研究了这种协同作用的普遍性。这些表面活性剂也引起了协同毒性，尽管反应的程度和时间框架取决于表面活性剂的结构。这些结果表明，需要进行额外的基础研究，以了解表面活性剂对纳米颗粒生物相容性的影响，并挑战传统的纳米颗粒安全性模型，其中假设基质对纳米颗粒毒性只有加性影响。
