In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

Wiemann, Martin; Sauer, Ursula G.; Vennemann, Antje; Bäcker, Sandra; Keller, Johannes-Georg; Ma‐Hock, Lan; Wohlleben, Wendel; Landsiedel, Robert

doi:10.3390/nano8030160

Cited by 24 publications

(40 citation statements)

References 101 publications

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“…For predicting the deposited dose, mostly the ISDD and DG models are employed. In line with our findings, it has been shown that both models predict the same ADs assuming sticky boundary conditions, meaning that particles adhere strongly to the surface [ 11 ]. However, in the case of weakly adhering surfaces, the DG model is better able to estimate deposition kinetics, which was experimentally validated by comparing calculated and quantified concentration profiles in frozen sections of columns of nanoparticle suspensions [ 9 ].…”

Section: Discussionsupporting

confidence: 90%

“…However, in the case of weakly adhering surfaces, the DG model is better able to estimate deposition kinetics, which was experimentally validated by comparing calculated and quantified concentration profiles in frozen sections of columns of nanoparticle suspensions [ 9 ]. However, verification of the ISDD and DG models at the single cell and particle level has not yet been performed [ 11 ]. Our SEM studies indicate that the ISDD and DG models correctly predict the deposited amount of silica particles for intercellular regions when emulating a “sticky” surface.…”

Section: Discussionmentioning

confidence: 99%

“…As the probability of a particle to adhere to the cell layer is neither 0 (reflective conditions) nor 1 (complete stickiness), modelling relies on user-defined assumptions for an ill-defined K D . So far, no methods have been developed to directly determine the relevant K D in different systems, which will depend on particle surface properties, and also on the cell type under investigation [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of in vitro particle dosimetry models at the single cell and particle level by scanning electron microscopy

et al. 2018

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BackgroundParticokinetic models are important to predict the effective cellular dose, which is key to understanding the interactions of particles with biological systems. For the reliable establishment of dose–response curves in, e.g., the field of pharmacology and toxicology, mostly the In vitro Sedimentation, Diffusion and Dosimetry (ISDD) and Distorted Grid (DG) models have been employed. Here, we used high resolution scanning electron microscopy to quantify deposited numbers of particles on cellular and intercellular surfaces and compare experimental findings with results predicted by the ISDD and DG models.ResultsExposure of human lung epithelial A549 cells to various concentrations of differently sized silica particles (100, 200 and 500 nm) revealed a remarkably higher dose deposited on intercellular regions compared to cellular surfaces. The ISDD and DG models correctly predicted the areal densities of particles in the intercellular space when a high adsorption (“stickiness”) to the surface was emulated. In contrast, the lower dose on cells was accurately inferred by the DG model in the case of “non-sticky” boundary conditions. Finally, the presence of cells seemed to enhance particle deposition, as aerial densities on cell-free substrates were clearly reduced.ConclusionsOur results further validate the use of particokinetic models but also demonstrate their limitations, specifically, with respect to the spatial distribution of particles on heterogeneous surfaces. Consideration of surface properties with respect to adhesion and desorption should advance modelling approaches to ultimately predict the cellular dose with higher precision.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0426-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of in vitro particle dosimetry models at the single cell and particle level by scanning electron microscopy

et al. 2018

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“…However, cytotoxicity appeared augmented in the high concentration range (which was different from the rightward shifted dose-response curves of FS, see below). It may be speculated that precipitated SAS re-agglomerate and settle more effectively at higher concentrations under cell culture conditions, and/or that smaller PS are more cytotoxic, as observed for colloidal SAS [50]. Also, the more pronounced formation of TNF in the mid concentration range could be due to increased numbers of smaller particles.…”

Section: Resultsmentioning

confidence: 99%

Effects of Ultrasonic Dispersion Energy on the Preparation of Amorphous SiO2 Nanomaterials for In Vitro Toxicity Testing

Wiemann¹,

Vennemann²,

Stintz

et al. 2018

Nanomaterials

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Synthetic amorphous silica (SAS) constitute a large group of industrial nanomaterials (NM). Based on their different production processes, SAS can be distinguished as precipitated, fumed, gel and colloidal. The biological activity of SAS, e.g., cytotoxicity or inflammatory potential in the lungs is low but has been shown to depend on the particle size, at least for colloidal silica. Therefore, the preparation of suspensions from highly aggregated or agglomerated SAS powder materials is critical. Here we analyzed the influence of ultrasonic dispersion energy on the biologic activity of SAS using NR8383 alveolar macrophage (AM) assay. Fully characterized SAS (7 precipitated, 3 fumed, 3 gel, and 1 colloidal) were dispersed in H2O by stirring and filtering through a 5 µm filter. Aqueous suspensions were sonicated with low or high ultrasonic dispersion (USD) energy of 18 or 270 kJ/mL, respectively. A dose range of 11.25–90 µg/mL was administered to the AM under protein-free conditions to detect particle-cell interactions without the attenuating effect of proteins that typically occur in vivo. The release of lactate dehydrogenase (LDH), glucuronidase (GLU), and tumor necrosis factor α (TNF) were measured after 16 h. Hydrogen peroxide (H2O2) production was assayed after 90 min. The overall pattern of the in vitro response to SAS (12/14) was clearly dose-dependent, except for two SAS which showed very low bioactivity. High USD energy gradually decreased the particle size of precipitated, fumed, and gel SAS whereas the low adverse effect concentrations (LOECs) remained unchanged. Nevertheless, the comparison of dose-response curves revealed slight, but uniform shifts in EC50 values (LDH, and partially GLU) for precipitated SAS (6/7), gel SAS (2/3), and fumed SAS (3/3). Release of TNF changed inconsistently with higher ultrasonic dispersion (USD) energy whereas the induction of H2O2 was diminished in all cases. Electron microscopy and energy dispersive X-ray analysis showed an uptake of SAS into endosomes, lysosomes, endoplasmic reticulum, and different types of phagosomes. The possible effects of different uptake routes are discussed. The study shows that the effect of increased USD energy on the in vitro bioactivity of SAS is surprisingly small. As the in vitro response of AM to different SAS is highly uniform, the production process per se is of minor relevance for toxicity.

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“…With respect to the mode of action, it is important that amorphous silica nanomaterials have a large specific surface of up to several hundred square meters per gram. It has been shown that the inflammatory effect of amorphous silica on the lung and also the cytotoxic effect on macrophages increases with surface size [ 4 ]. Of note, the inflammatory effect of colloidal SiO 2 can be reduced by surface coating with amino or phosponate residues [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Distribution of Paramagnetic Fe2O3/SiO2–Core/Shell Nanoparticles in the Rat Lung Studied by Time-of-Flight Secondary Ion Mass Spectrometry: No Indication for Rapid Lipid Adsorption

Veith¹,

Vennemann²,

Breitenstein³

et al. 2018

Nanomaterials

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Amorphous silica nanoparticles comprise a class of widely used industrial nanomaterials, which may elicit acute inflammation in the lung. These materials have a large specific surface to which components of the pulmonary micro-milieu can bind. To conduct appropriate binding studies, paramagnetic Fe2O3/SiO2 core/shell nanoparticles (Fe-Si-NP) may be used as an easy-to-isolate silica surrogate, if several prerequisites are fulfilled. To this end, we investigated the distribution of Fe, Si, protein and phosphatidylcholine (PC) by Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) in cryo-sections from the rat lungs to which Fe-Si-NP had been administered for 30 min. Regions-of-interest were identified and analyzed with incident light and enhanced dark-field microscopy (DFM). Fe-Si-NP particles (primary particle size by electron microscopy: 10–20 nm; aggregate size by tracking analysis: 190 ± 20 nm) and agglomerates thereof were mainly attached to alveolar walls and only marginally internalized by cells such as alveolar macrophages. The localization of Fe-Si-NP by DFM was confirmed by ToF-SIMS signals from both, Fe and Si ions. With respect to an optimized signal-to-noise ratio, Fe+, Si+, CH4N+ and the PC head group (C5H15NO4P+) were the most versatile ions to detect iron, silica, protein, and PC, respectively. Largely congruent Fe+ and Si+ signals demonstrated that the silica coating of Fe-Si-NP remained stable under the conditions of the lung. PC, as a major lipid of the pulmonary surfactant, was colocalized with the protein signal alongside alveolar septa, but was not detected on Fe-Si-NP, suggesting that silica nanoparticles do not adsorb lipids of the lung surfactant under native conditions. The study shows that ToF-SIMS is a valuable technique with adequate spatial resolution to analyze nanoparticles together with organic molecules in the lung. The paramagnetic Fe-Si-NP appear well suited to study the binding of proteins to silica nanomaterials in the lung.

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In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

Cited by 24 publications

References 101 publications

Assessment of in vitro particle dosimetry models at the single cell and particle level by scanning electron microscopy

Assessment of in vitro particle dosimetry models at the single cell and particle level by scanning electron microscopy

Effects of Ultrasonic Dispersion Energy on the Preparation of Amorphous SiO2 Nanomaterials for In Vitro Toxicity Testing

Distribution of Paramagnetic Fe2O3/SiO2–Core/Shell Nanoparticles in the Rat Lung Studied by Time-of-Flight Secondary Ion Mass Spectrometry: No Indication for Rapid Lipid Adsorption

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