Toxicological effects of zinc oxide nanoparticle exposure: an <i>in vitro</i> comparison between dry aerosol air-liquid interface and submerged exposure systems

Lovén, Karin; Dobric, Julia; Bölükbas, Deniz A.; Kåredal, Monica; Taş, Sinem; Rissler, Jenny; Wagner, Darcy E.; Isaxon, Christina

doi:10.1080/17435390.2021.1884301

Cited by 12 publications

(5 citation statements)

References 52 publications

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“…Unlike a number of in vitro studies that report strong cytotoxicity of applied Ag-NP suspensions, Ag-NP applied as an aerosol to cells cultured at ALI is negligibly cytotoxic and only induces mild inflammatory effects. [69,70] It has been shown in many nanotoxicity studies that aerosol exposure induces different biological answers than submerged exposures, [58,62,71,72] which is in line with the results of this study. In addition to the study of cell viability, the morphology of the cells was investigated via TEM and SEM.…”

Section: Effect Of Agnp and Cnc On Ali Culture In 96-well Formatsupporting

confidence: 91%

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Kohl

Müller

Fink³

et al. 2023

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In this study, a 96‐well exposure system for safety assessment of nanomaterials is developed and characterized using an air–liquid interface lung epithelial model. This system is designed for sequential nebulization. Distribution studies verify the reproducible distribution over all 96 wells, with lower insert‐to‐insert variability compared to non‐sequential application. With a first set of chemicals (TritonX), drugs (Bortezomib), and nanomaterials (silver nanoparticles and (non‐)fluorescent crystalline nanocellulose), sequential exposure studies are performed with human lung epithelial cells followed by quantification of the deposited mass and of cell viability. The developed exposure system offers for the first time the possibility of exposing an air–liquid interface model in a 96‐well format, resulting in high‐throughput rates, combined with the feature for sequential dosing. This exposure system allows the possibility of creating dose‐response curves resulting in the generation of more reliable cell‐based assay data for many types of applications, such as safety analysis. In addition to chemicals and drugs, nanomaterials with spherical shapes, but also morphologically more complex nanostructures can be exposed sequentially with high efficiency. This allows new perspectives on in vivo‐like and animal‐free approaches for chemical and pharmaceutical safety assessment, in line with the 3R principle of replacing and reducing animal experiments.

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Section: Effect Of Agnp and Cnc On Ali Culture In 96-well Formatsupporting

confidence: 91%

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Kohl

Müller

Fink³

et al. 2023

Small

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“…This was not identified in our study; in fact the IL-8 concentration was ~100 times higher in the VitroCell exposures (Figure 6B) when compared to the quasi-ALI exposures (Figure 4B) in the static model and ~150 times higher in the fluid flow exposures (Figures 4B and 6B) after exposure to both the highest concentrations of DQ 12 and TiO 2 . This has also been identified using ZnO ENPs (at 1 µg/cm 2 ) and an aerosol and "traditional" exposures using A549 cells [72]. The same was also true for IL-6 concentrations after exposure to the higher concentrations of DQ 12 and TiO 2 there was a ~5 and ~3 times increase, respectively, after VitroCell exposure compared to quasi-ALI exposures.…”

Section: Quasi-ali and Aerosol Exposuressupporting

confidence: 55%

Dynamic Fluid Flow Exacerbates the (Pro-)Inflammatory Effects of Aerosolised Engineered Nanomaterials In Vitro

Meldrum

Doak

et al. 2022

Nanomaterials

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The majority of in vitro studies focusing upon particle–lung cell interactions use static models at an air–liquid interface (ALI). Advancing the physiological characteristics of such systems allows for closer resemblance of the human lung, in turn promoting 3R strategies. PATROLS (EU Horizon 2020 No. 760813) aimed to use a well-characterised in vitro model of the human alveolar epithelial barrier to determine how fluid-flow dynamics would impact the outputs of the model following particle exposure. Using the QuasiVivoTM (Kirkstall Ltd., York, UK) system, fluid-flow conditions were applied to an A549 + dTHP-1 cell co-culture model cultured at the ALI. DQ12 and TiO2 (JRCNM01005a) were used as model particles to assess the in vitro systems’ sensitivity. Using a quasi- and aerosol (VitroCell Cloud12, VitroCell Systems, Waldkirch, Germany) exposure approach, cell cultures were exposed over 24 h at IVIVE concentrations of 1 and 10 (DQ12) and 1.4 and 10.4 (TiO2) µg/cm2, respectively. We compared static and fluid flow conditions after both these exposure methods. The co-culture was subsequently assessed for its viability, membrane integrity and (pro-)inflammatory response (IL-8 and IL-6 production). The results suggested that the addition of fluid flow to this alveolar co-culture model can influence the viability, membrane integrity and inflammatory responses dependent on the particle type and exposure.

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“…higher response at the same dose or lower dose for the same level of response), the opposite or equivocal results. There is similar distribution of studies that have strongest effect in ALI (four studies; Loret et al, 2016 ; Hilton et al, 2019 ; Diabaté et al, 2021 : Lovén et al, 2021 ), strongest effect in submerged condition (three studies; Herzog et al, 2014 ; Panas et al, 2014 ; Mills‐Goodlet et al, 2020 ) and equivocal outcome of the comparison between ALI and submerged condition (six studies; Lenz et al, 2009 ; Lenz et al, 2013 ; Stoehr et al, 2015 ; Cappellini et al, 2020 ; Medina‐Reyes et al, 2020 ; Di Ianni, Erdem, et al, 2021 ). This suggests that it is presently unclear whether the magnitude of effects with the ALI system is higher and whether such exposure systems are superior to submerged conditions.…”

Section: Perspectivesmentioning

confidence: 83%

Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives

Ianni

Jacobsen

Vogel

et al. 2022

WIREs Nanomed Nanobiotechnol

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Animal experiments are highly relevant models for the assessment of toxicological effects of engineered nanomaterials (ENMs), due to lack of biomonitoring and epidemiological studies. However, the expanding number of ENMs with different physico‐chemical properties strains this approach, as there are ethical concerns and economical challenges with the use of animals in toxicology. There is an urgent need for cell culture models that predict the level of toxicological responses in vivo, consequently reducing or replacing the use of animals in nanotoxicology. However, there is still a limited number of studies on in vitro–in vivo correlation of toxicological responses following ENMs exposure. In this review, we collected studies that have compared in vitro and in vivo toxic effects caused by ENMs. We discuss the influence of cell culture models and exposure systems on the predictability of in vitro models to equivalent toxic effects in animal lungs after pulmonary exposure to ENMs. In addition, we discuss approaches to qualitatively or quantitatively compare the effects in vitro and in vivo. The magnitude of toxicological responses in cells that are exposed in submerged condition is not systematically different from the response in cells exposed in air–liquid interface systems, and there appears to be similar ENMs hazard ranking between the two exposure systems. Overall, we show that simple in vitro models with cells exposed to ENMs in submerged condition can be used to predict toxic effects in vivo, and identify future strategies to improve the associations between in vitro and in vivo ENMs‐induced pulmonary toxicity. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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Toxicological effects of zinc oxide nanoparticle exposure: an in vitro comparison between dry aerosol air-liquid interface and submerged exposure systems

Abstract: Isaxon (2021): Toxicological effects of zinc oxide nanoparticle exposure: an in vitro comparison between dry aerosol air-liquid interface and submerged exposure systems, Nanotoxicology,

Cited by 12 publications

References 52 publications

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Dynamic Fluid Flow Exacerbates the (Pro-)Inflammatory Effects of Aerosolised Engineered Nanomaterials In Vitro

Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives

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