Biological and Environmental Transformations of Copper-Based Nanomaterials

Abstract

Copper-based nanoparticles are an important class of materials with applications as catalysts, conductive inks, and antimicrobial agents. Environmental and safety issues are particularly important for copper-based nanomaterials because of their potential large-scale use and their high redox activity and toxicity reported from in vitro studies. Elemental nanocopper oxidizes readily upon atmospheric exposure during storage and use, so copper oxides are highly relevant phases to consider in studies of environmental and health impacts. Here we show that copper oxide nanoparticles undergo profound chemical transformations under conditions relevant to living systems and the natural environment. Copper oxide nanoparticle (CuO-NP) dissolution occurs at lysosomal pH (4-5), but not at neutral pH in pure water. Despite the near-neutral pH of cell culture medium, CuO-NPs undergo significant dissolution in media over time scales relevant to toxicity testing due to ligand-assisted ion release, in which amino acid complexation is an important contributor. Electron paramagnetic resonance (EPR) spectroscopy shows that dissolved copper in association with CuO-NPs are the primary redox-active species. CuO-NPs also undergo sulfidation by a dissolution-reprecipitation mechanism, and the new sulfide surfaces act as catalysts for sulfide oxidation. Copper sulfide NPs are found to be much less cytotoxic than CuO NPs, which is consistent with the very low solubility of CuS. Despite this low solubility of CuS, EPR studies show that sulfidated CuO continues to generate some ROS activity due to the release of free copper by H2O2 oxidation during the Fenton-chemistry-based EPR assay. While sulfidation can serve as a natural detoxification process for nanosilver and other chalcophile metals, our results suggest that sulfidation may not fully and permanently detoxify copper in biological or environmental compartments that contain reactive oxygen species.

Comparative environmental fate and toxicity of copper nanomaterials

“…Highly aggregated Cu NPs have a reduced surface area, which decreases the dissolution rate. In simple salt solutions, dissolution rate was nCu(OH) 2 -b > nCu ≫ nCuO, and in all cases, the dissolution rate decreased as pH increased from 4 to 11 Wang et al, 2013). Dissolution of Cu NPs was enhanced at high IS in the presence of NOM due to additional complexation.…”

Central nervous system toxicity of metallic nanoparticles

“…Furthermore, high intracellular calcium levels caused by NPs may also serve as an alternative mechanism for the activation of these mechanisms. 84 Domenech et al 85 found that IO MNPs are capable of inducing lysosome LMP in cells. Yang et al 86 used both acridine orange staining and transmission electron microscopy (TEM) images to confirm that the accumulation of carbon nanohorns (CNHs) in the lysosomes induced LMP.…”

Sulfidation as a Natural Antidote to Metallic Nanoparticles Is Overestimated: CuO Sulfidation Yields CuS Nanoparticles with Increased Toxicity in Medaka (Oryzias latipes) Embryos

“…In previous studies, 25,32,33 copper ions and CuS particles have been proven to be able to catalyze the HS − oxidation under oxygen-presence conditions. Here a depletion of DO upon addition of copper ions or CuS-NPs generated from the sulfidation to Na 2 S solution was also observed.…”

“…The X (9.8 GHz)-band EPR analyses using an EMX-plus CW spectrometer (Bruker Biospin) and the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO, Sigma-Aldrich, U.S.A.) could show a relative reactive oxygen species (ROS) intensity by observing peak height. The analyses were performed following the method as previously described by Wang et al 25 Briefly, 10 mg/L copper particles or CuSO 4 were mixed with DMPO (100 mM) and H 2 O 2 (1 mM) in buffer for 20 min. The reaction was triggered by the addition of H 2 O 2 .…”

“…19−22 CuS particles were reported to be much less cytotoxicity than CuO particles due to the low solubility of CuS in cell culture media [i.e., Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with 10% fetal bovine serum (FBS) ]. 25 Nevertheless, previous study 25 was conducted in cell culture media with 5 mg/L particles rather than aqueous solutions where aquatic organisms are indeed daily exposed to the particles at environmentally relevant concentrations. Also, even if CuS released copper ions, due to the presence of phosphate in cell culture media, the formation of copper phosphate with lower solubility than CuS could mitigate the cytotoxicity, which would overestimate the detoxification contributions from sulfidation.…”