Abstract
Nanoparticles (NPs) may affect the lung via their chemical composition on the surface. Here, we compared the bioactivity of zirconium oxide (ZrO2) NPs coated with either aminopropilsilane (APTS), tetraoxidecanoic acid (TODS), polyethyleneglycol (PGA), or acrylic acid (Acryl). Supernatants from NPs-treated cultured alveolar macrophages (NR8383) tested for lactate dehydrogenase, glucuronidase, tumor necrosis factor α, and H2O2 formation revealed dose-dependent effects, with only gradual differences among particles whose gravitational settling and cellular uptake were similar. We selected TODS- and Acryl-coated NPs for intratracheal administration into the rat lung. Darkfield and hyperspectral microscopy combined with immunocytochemistry showed that both NPs qualities accumulate mainly within the alveolar macrophage compartment, although minute amounts also occurred in neutrophilic granulocytes. Dose-dependent signs of inflammation were found in the broncho-alveolar lavage fluid on day 3 but no longer on day 21 post-application of ≥1.2 mg per lung; again only minor differences occurred between TODS- and Acryl-coated NPs. In contrast, the response of allergic mice was overall higher compared to control mice and dependent on the surface modification. Increases in eosinophils, lymphocytes and macrophages were highest following ZrO2-PGA administration, followed by ZrO2-Acryl, ZrO2-TODS, and ZrO2-APTS. We conclude that surface functionalization of ZrO2 NPs has minor effects on the inflammatory lung response of rats and mice, but is most relevant for an allergic mouse model. Allergic individuals may therefore be more susceptible to exposure to NPs with specific surface modifications.
Highlights
The inhalation of airborne nanomaterials may lead to adverse health effects in the lung such as inflammation, granule formation, or even genotoxic effects [1,2,3]
Our study shows that the coating of ZrO2 NPs with APTS, TODS, Acryl, or PGA has little influence on the bioactivity of ZrO2 NPs in the macrophage assay or the rat lung
As we tested the ability of different surface modifications to mitigate the pro-inflammatory and immunomodulatory effects of SiO2-NPs in a similar model of lung allergic inflammation, we demonstrated that PGA-coated NPs exert a strong adjuvant effect, augmenting the type 2 helper cell (Th2) pro-inflammatory milieu caused by uncoated SiO2 particles [10]
Summary
The inhalation of airborne nanomaterials may lead to adverse health effects in the lung such as inflammation, granule formation, or even genotoxic effects [1,2,3]. The chemical nature of the NPs surface may, indirectly influence the biodistribution and effects of NPs in the body. Various coatings of colloidal silica NPs with a mean size of 15 nm can influence the inflammatory properties of the core material both in vitro and in vivo [8,9,10]. I.e., uncoated material elicited inflammatory effects upon inhalation and administration, coating with phosphonate, amine, or polyethylene glycol residues gradually abrogated cytotoxic and inflammogenic effects in the rat lung [9,10]. Phosphonate or silica coating mitigated the toxic effects of other metal oxide particles [11,12], suggesting that a chemical shielding of the nanoparticle surface can downregulate its toxic or inflammatory effects
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