Chemical Transformations of Nanosilver in Biological Environments

Department of Chemistry, ‡School of Engineering, §Department of Pathology and Laboratory Medicine, and ⊥Institute for Molecular and Nanoscale Innovation, Brown University , Providence, Rhode Island 02912, United States.
ACS Nano (Impact Factor: 12.88). 10/2012; 6(11). DOI: 10.1021/nn303449n
Source: PubMed


The widespread use of silver nanoparticles (Ag-NPs) in consumer and medical products provides strong motivation for a careful assessment of their environmental and human health risks. Recent studies have shown that Ag-NPs released to the natural environment undergo profound chemical transformations that can affect silver bioavailability, toxicity, and risk. Less is known about Ag-NP chemical transformations in biological systems, though the medical literature clearly reports that chronic silver ingestion produces argyrial deposits consisting of silver-, sulfur-, and selenium-containing particulate phases. Here we show that Ag-NPs undergo a rich set of biochemical transformations, including accelerated oxidative dissolution in gastric acid, thiol binding and exchange, photoreduction of thiol- or protein-bound silver to secondary zerovalent Ag-NPs, and rapid reactions between silver surfaces and reduced selenium species. Selenide is also observed to rapidly exchange with sulfide in preformed Ag(2)S solid phases. The combined results allow us to propose a conceptual model for Ag-NP transformation pathways in the human body. In this model, argyrial silver deposits are not translocated engineered Ag-NPs, but rather secondary particles formed by partial dissolution in the GI tract followed by ion uptake, systemic circulation as organo-Ag complexes, and immobilization as zerovalent Ag-NPs by photoreduction in light-affected skin regions. The secondary Ag-NPs then undergo detoxifying transformations into sulfides and further into selenides or Se/S mixed phases through exchange reactions. The formation of secondary particles in biological environments implies that Ag-NPs are not only a product of industrial nanotechnology but also have long been present in the human body following exposure to more traditional chemical forms of silver.

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Available from: Jingyu Liu, Dec 11, 2014
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    • "However, these ions can be substituted for other metal ions such as Ag, Cu, Cd, Hg, Pb and Fe and protect cells against the toxicity of these metals. It is known that cysteine, and more generally thiol-containing molecules, are extremely strong binding ligands for Ag ions (Adams and Kramer, 1999; Liu et al., 2012). "
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    ABSTRACT: Large knowledge gaps still exist on the toxicological mechanisms of silver (Ag) engineered nanoparticles (ENPs); a comprehensive understanding of the sources, biodistribution, toxicity and transformation of Ag ENPs along their life cycle and after transfer in living organisms is needed. In a previous study, mice were pulmonary exposed to Ag ENPs and local (lung) and systemic toxic effects together with biodistribution to organs including heart, liver, spleen and kidney were investigated. Here, Ag lung distribution, local concentration, co-localization with other elements such as Fe, Cu and S, and speciation were determined after lung exposure to Ag ENPs using micro X-ray fluorescence (μXRF), micro X-ray absorption near edge structure spectroscopy (μXANES) and micro proton-induced X-ray emission (μPIXE) techniques. We found that approximately a quarter of all macrophages in the lumen of the airways contained ENPs. High local concentrations of Ag were also detected in the lung tissue, probably phagocytized by macrophages. The largest part of the ENPs was dissolved and complexed to thiol-containing molecules. Increased concentrations of Fe and Cu observed in the Ag-rich spots suggest that these molecules are metallothioneins (MTs). . These results give more insights on the behavior of Ag ENPs in the lung in vivo and will help in the understanding of the toxicological mechanisms of Ag ENPs. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology Letters 07/2015; 238(1). DOI:10.1016/j.toxlet.2015.07.001 · 3.26 Impact Factor
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    • "Silver nanoparticles have attracted a great deal of attention owing their applications in catalysis, sensors, electronics, biomedicine and other fields [1] [2] [3] [4] [5], which are based on specific properties of nanoparticles and depend upon their size, shape, stabilizing agents, aggregation, support, and so on. The oxidation of Ag NPs in aqueous media affording silver oxides or dissolved metal ions is also of considerable fundamental and practical interest for understanding the biological activity and environmental impacts of nanosilver [6] [7] [8] [9]. The O and Ag species on Ag NPs have been widely explored in relation to catalysis using X-ray and UV photoelectron spectroscopy and other surface science techniques [10] [11] [12] [13] [14], mainly at low oxygen pressure. "
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    ABSTRACT: Many applications and environmental impact of silver-bearing nanomaterials critically depend upon their specific reactivity, which is still poorly understood. Here, silver nanoparticles (Ag NPs) of about 3─5 nm and 10─12 nm in diameter, uncapped and capped with L-glucose or citrate, were prepared, characterized using UV─vis absorption spectroscopy, SAXS, TEM, and their (electro)chemical oxidation was examined in comparison with each other and bulk metal applying scanning tunneling microscopy and spectroscopy, cyclic voltammetry, and XPS. A resistive switching effect was found in the tunneling spectra measured in air at the smaller uncapped Ag NPs deposited on HOPG and was interpreted in terms of Ag transfer between the particle and the probe. The anodic oxidation of these Ag NPs in 1 M NaOH yielded 3D Ag2O, while only a layer of "primary" Ag(I) oxide emerged on larger uncapped nanoparticles during the potential sweep. The formation of AgO at higher potentials proceeded readily at the "primary" oxide but was retarded at the smaller NPs. The citrate- and glucose-capping substantially impeded the formation both of Ag2O and AgO. The findings highlighted, particularly, a non-trivial effect of particle size and transient mobilization of Ag species on the reactions of silver nanoparticles.
    Applied Surface Science 04/2014; 297:75–83. DOI:10.1016/j.apsusc.2014.01.081 · 2.71 Impact Factor
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    • "This is in line with previous reports showing that the release of Ag is directly related to the total surface of the particles as well as the composition of the experimental media [47]. Ag release has previously been reported to increase with smaller particle size in a non-linear manner [48], thus explaining the much higher release from the 10 nm particles when compared to the other sizes. To further explore the role of the released Ag, we also investigated the toxicity of the “released fraction” (i.e. the supernatant of centrifuged particles after incubation in cell medium for 24 h thus likely containing various Ag-complexes). "
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    ABSTRACT: Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and gammaH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no gammaH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4-7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a 'Trojan horse' effect.
    Particle and Fibre Toxicology 02/2014; 11(1):11. DOI:10.1186/1743-8977-11-11 · 7.11 Impact Factor
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