Differential Effects of Surface-Functionalized Zirconium Oxide Nanoparticles on Alveolar Macrophages, Rat Lung, and a Mouse Allergy Model

• Main Authors: Antje Vennemann, Francesca Alessandrini, Martin Wiemann
• Format: Article
• Language: English
• Published: MDPI AG 2017-09-01
• Series: Nanomaterials
• Subjects: macrophage model; intratracheal administration; ZrO2 nanoparticles; inflammation; surface labelling; polyethylene glycol; allergy
• Online Access: https://www.mdpi.com/2079-4991/7/9/280

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.