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.
    Full-text · Article · Jul 2015 · Toxicology Letters
    • "Upon uptake into cells the release of Ag þ is increased compared with water-suspended AgNPs (Singh and Ramarao, 2012). This increase in dissolution is likely due to various intracellular mechanisms including changes in pH, oxidative interactions, and/or complexation with intracellular proteins, especially those with thiol groups (Liu et al., 2012; Singh and Ramarao, 2012). It is currently unclear how the addition of the PC may influence mechanisms of dissolution of AgNPs both extracellularly and intracellularly. "
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    ABSTRACT: Addition of a protein corona (PC) or protein adsorption layer on the surface of nanomaterials following their introduction into physiological environments may modify their activity, bio-distribution, cellular uptake, clearance and toxicity. We hypothesize that silver nanoparticles (AgNPs) will associate with proteins common to human serum and cell culture media forming a PC that will impact cell activation and cytotoxicity. Furthermore, the role of scavenger receptor BI (SR-BI) in mediating this toxicity was evaluated. Citrate-suspended 20 nm AgNPs were incubated with human serum albumin (HSA), bovine serum albumin (BSA), high-density lipoprotein (HDL), or water (control) to form a PC. AgNPs associated with each protein (HSA, BSA, HDL) forming PCs as assessed by electron microscopy, hyperspectral analysis, ζ-potential, and hydrodynamic size. Addition of the PC decreased uptake of AgNPs by rat lung epithelial (RLE) and rat aortic endothelial (RAEC) cells. Hyperspectral analysis demonstrated a loss of the AgNP PC following internalization. Cells demonstrated concentration-dependent cytotoxicity following exposure to AgNPs with or without PCs (0, 6.25, 12.5, 25 or 50 μg/ml). All PC-coated AgNPs were found to activate cells by inducing IL-6 mRNA expression. A small molecule SR-BI inhibitor was utilized to determine the role of SR-BI in the observed effects. Pretreatment with the SR-BI inhibitor decreased internalization of AgNPs with or without PCs, and reduced both cytotoxicity and IL-6 mRNA expression. This study characterizes the formation of a PC on AgNPs and demonstrates its influence on cytotoxicity and cell activation through a cell surface receptor.
    No preview · Article · Oct 2014 · Toxicological Sciences
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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.
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