Dissolution Behaviour of Metal-Oxide Nanomaterials in Various Biological Media

Abstract

Toxicological effects of metal-oxide-engineered nanomaterials (ENMs) are closely related to their distinct physical–chemical properties, especially solubility and surface reactivity. The present study used five metal-oxide ENMs (ZnO, MnO2, CeO2, Al2O3, and Fe2O3) to investigate how various biologically relevant media influenced dissolution behaviour. In both water and cell culture medium (DMEM), the metal-oxide ENMs were more soluble than their bulk analogues, with the exception that bulk-MnO2 was slightly more soluble in water than nano-MnO2 and Fe2O3 displayed negligible solubility across all tested media (regardless of particle size). Lowering the initial concentration (10 mg/L vs. 100 mg/L) significantly increased the relative solubility (% of total concentration) of nano-ZnO and nano-MnO2 in both water and DMEM. Nano-Al2O3 and nano-CeO2 were impacted differently by the two media (significantly higher % solubility at 10 mg/L in DMEM vs. water). Further evaluation of simulated interstitial lung fluid (Gamble’s solution) and phagolysosomal simulant fluid (PSF) showed that the selection of aqueous media significantly affected agglomeration and dissolution behaviour. The solubility of all investigated ENMs was significantly higher in DMEM (pH = 7.4) compared to Gamble’s (pH 7.4), attributable to the presence of amino acids and proteins in DMEM. All ENMs showed low solubility in Gamble’s (pH = 7.4) compared with PSF (pH = 4.5), attributable to the difference in pH. These observations are relevant to nanotoxicology as increased nanomaterial solubility also affects toxicity. The results demonstrated that, for the purpose of grouping and read-across efforts, the dissolution behaviour of metal-oxide ENMs should be evaluated using aqueous media representative of the exposure pathway being considered.

Toxicity of Metal Oxide Nanoparticles: Looking through the Lens of Toxicogenomics

“…Similar analyte loss during control experiments was reported by Avramescu et al, 2023 [32] at a lower AlCl 3 concentration of 1 mg/L. Considering the observed analyte loss, the authors suggested that the solubility reported may be considered an 'apparent solubility', which represents the portion of released Al that is not matrix bound [32]. Furthermore, particle formation has been noted by others when conducting in vitro exposures using AlCl 3 as well as within simulated intestinal fluid [38,39].…”

“…Dissolution testing for all relevant MONPs and MOMPs was carried out by Avramescu et al, 2020 [ 31 ] and Avramescu et al, 2023 [ 32 ], the results of which were used to inform the toxicity testing conducted in the present study ( Table S1 ). MONPs were grouped as negligible (<1% dissolved), low (1–10% dissolved), moderate (10–70% dissolved), or highly soluble (>70% dissolved) according to Avramescu et al, 2023 [ 32 ], which was based on criteria reported in ENV/JM/MONO (2015) [ 35 ].…”

“…Oxidative stress and unfolded protein responses were commonly seen in Zn, Cu, and Ni-exposed cells and, to a lesser extent, in TiO 2 NP exposed cells; however, important pathways implicated in glycolysis were for the most part not enriched (Supplementary Document S1). NiO NPs exhibit low-negligible solubility in cell culture medium [32] and moderate-low solubility in acidic environments [51], with dissolved Ni shown to induce a state of cellular hypoxia akin to the hypoxia-mimetic compound cobalt chloride [52,53]. Transcriptional induction of hypoxia was seen for NiO NPs, MPs, and NiCl 2 , which all enriched and activated 'HIF-1α Signaling', in addition to activation of glycolysis for all Ni compounds and inactivation of oxidative phosphorylation for NiO NPs and NiCl 2 (Supplementary Document S1, Supplementary File S3).…”

“…Previous research has shown that MONP dissolution is a function of time, particle concentration, particle size, chemical composition, and the solvent medium [ 31 , 32 ]. Due to the time-dependent nature of dissolution, the toxicity of soluble MONPs is a function of both the particulate and dissolved species, whereas MONPs with negligible solubility induce toxicity through interactions with the particle surface.…”

The effect of metal oxide coating of urea on mineralization in two contrasting soils

“…Although zinc oxide (ZnO)‐coated urea has been tested as a Zn fertilizer (Milani et al., 2015), neither copper oxide (CuO) nor nickel oxide (NiO) has been used before as a coating material and none of the metal oxides have been tested to inhibit urea hydrolysis. These oxides are usually produced in the <100 μm particle size range and are highly insoluble in water, which might provide an added effect when used as a binder of delaying the dissolution of the urea core in addition to inhibiting urea hydrolysis (Avramescu et al., 2023; Irfan et al., 2018).…”