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

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.

Silver Nanoparticles in the Lung: Toxic Effects and Focal Accumulation of Silver in Remote Organs

“…A mitigating influence of serum has been documented also for other nanoparticles in vitro, such as amorphous SiO 2 [ 31 ]. Trying to extrapolate the lung burden leading to mild toxicity from the lowest toxic in vitro dose via the alveolar macrophage number per lung, a procedure which had yielded an acceptable approximation in instillation experiments, e.g., with ZrO 2 NP [ 32 ], apparently overestimated the low observed adverse effect level (LOAEC). It appears possible that macrophages are less sensitive to Ag-NP or Ag ions than lung epithelial cells, but this assumption is contradicted by our own and other experiments in which phagocytic cells accumulating NP reacted more sensitively than non-phagocytic cells [ 33 ].…”

Lung Toxicity Analysis of Nano-Sized Kaolin and Bentonite: Missing Indications for a Common Grouping

“…The cell viability was determined by trypan blue testing. Differential cell counts of at least 400 cells per animal were obtained after May-Grünwald and Giemsa staining of cytospin preparations, as described [23]. The total BALF protein was measured with the Lowry method, using bovine serum albumin as a standard.…”

“…A single dose of 1.2 mg per rat lung was chosen to compare the effects of bentonite, kaolin, and quartz DQ12 in vivo. This dose had been successfully used to obtain significant changes in previous experiments with quartz DQ12 as a positive control [23]. The same dose may also be estimated from the most effective concentration of kaolin in vitro (180 µg/mL, i.e., 36 µg/well), which calculates to a mean cellular dose of 120 pg/cell (36 µg divided by 3 × 10 5 cells per well).…”

Detection of ZrO2 Nanoparticles in Lung Tissue Sections by Time-of-Flight Secondary Ion Mass Spectrometry and Ion Beam Microscopy

“…Thirdly, the study, which is part of the special issue on “Nanoparticles in Vivo and in Vitro Studies: a Collection of Parallel Approaches”, shall also contribute to our understanding of the toxicological relevance of ZrO 2 NP in the lung, which acts as the main entry port for airborne nanomaterials into the body. ZrO 2 NP are used in coatings of self-cleaning stoves, in dental filler material, or implant materials [ 5 ], and the toxic effects of differentially coated ZrO 2 NP on alveolar macrophages and on rat and allergic mouse lung have been described in an accompanying publication [ 6 ]. Of note, ZrO 2 NP administered to the lung has been previously located mainly within alveolar macrophages by Raman microspectroscopy, hyperspectral microscopy, and immunocytochemistry [ 6 , 7 ].…”

“…ZrO 2 NP are used in coatings of self-cleaning stoves, in dental filler material, or implant materials [ 5 ], and the toxic effects of differentially coated ZrO 2 NP on alveolar macrophages and on rat and allergic mouse lung have been described in an accompanying publication [ 6 ]. Of note, ZrO 2 NP administered to the lung has been previously located mainly within alveolar macrophages by Raman microspectroscopy, hyperspectral microscopy, and immunocytochemistry [ 6 , 7 ]. The present study comparing IBM and ToF-SIMS analyses of ZrO 2 NP distribution was carried out on rat lung tissue from this previous study [ 6 ].…”