Parametric Optimization of an Air–Liquid Interface System for Flow-Through Inhalation Exposure to Nanoparticles: Assessing Dosimetry and Intracellular Uptake of CeO2 Nanoparticles

Leibrock, Lars; Jungnickel, Harald; Tentschert, Jutta; Katz, Aaron; Toman, Blaza; Petersen, Elijah J.; Bierkandt, Frank S.; Singh, Ajay; Laux, Peter; Luch, Andreas

doi:10.3390/nano10122369

Cited by 28 publications

(41 citation statements)

References 82 publications

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“…In order to reproduce a more realistic exposure scenario, maintaining the conditions of temperature and humidity in physiological levels needed in the cell culture, the Vitrocell Cloud system coupled to an AeroNeb Lab nebulizer was used for exposure of the cells to CeO 2 -NPs. Other authors have already demonstrated the suitability of this system to reproduce an inhalation scenario and have demonstrated that A549 cells in vitro are able to uptake similar concentrations of CeO 2 -NPs as those taken up in vivo [ 62 ]. During the exposures, the Vitrocell Cloud system produced a very homogeneous deposition of CeO 2 -NPs onto the cells similar to previous studies [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

et al. 2021

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Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, the toxicological effects of these ENMs should be further studied. In this study, the acute and subchronic toxicity of CeO2-NPs were assessed. First, an in vitro multi-dose short-term (24 h) toxicological assessment was performed in three different cell lines: A549 and Calu3 were used to represented lung tissue and 3T3 was used as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well-established reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air–Liquid Interface (ALI), to study the long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENMs, highlighting the need for subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in organisms.

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Section: Discussionmentioning

confidence: 99%

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

et al. 2021

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“… 28 , 35 , 36 , 42 , 54 , 56 The influence of nanomedicine on cellular architecture can be assessed by a pragmatic optimized air–liquid interface system, which showed comparable results as those in an in vivo study. 90 …”

Section: Cellular Targets For Nanomedicinementioning

confidence: 99%

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

Bian¹,

Cai²,

Cui³

et al. 2021

IJN

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Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) may lead to a life-threatening form of respiratory failure, resulting in high mortality of up to 30-40% in most studies. Although there have been decades of research since ALI was first described in 1967, the clinical therapeutic alternatives for ALI are still in a state of limited availability. Supportive treatment and mechanical ventilation still have priority. Despite some preclinical studies demonstrating the benefit of pharmacological interventions, none of these has been proved completely effective to date. Recent advances in nanotechnology may shed new light on the pharmacotherapy of ALI. Nanomedicine possesses targeting and synergistic therapeutic capability, thus boosting pharmaceutical efficacy and mitigating the side effects. Currently, a variety of nanomedicine with diverse frameworks and functional groups have been elaborately developed, in accordance with their lung targeting ability and the pathophysiology of ALI. The in-depth review of the current literature reveals that liposomes, polymers, inorganic materials, cell membranes, platelets, and other nanomedicine approaches have conferred attractive therapeutic benefits for ALI treatment. In this review, we explore the recent progress in the study of the nanomedicinebased therapy of ALI, presenting various nanomedical approaches, drug choices, therapeutic strategies, and outcomes, thereby providing insight into the trends.

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“…Statistical analysis of the ToF-SIMS data was performed as described in detail elsewhere [33,34]. In brief, the acquired data were binned to 1 mass unit (u).…”

Section: Statistical Analysis Of the Tof-sims Datamentioning

confidence: 99%

Combinatory Effects of Cerium Dioxide Nanoparticles and Acetaminophen on the Liver—A Case Study of Low-Dose Interactions in Human HuH-7 Cells

Krause

Kriegel

Tartz

et al. 2021

IJMS

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The interactions between pharmaceuticals and nanomaterials and its potentially resulting toxicological effects in living systems are only insufficiently investigated. In this study, two model compounds, acetaminophen, a pharmaceutical, and cerium dioxide, a manufactured nanomaterial, were investigated in combination and individually. Upon inhalation, cerium dioxide nanomaterials were shown to systemically translocate into other organs, such as the liver. Therefore we picked the human liver cell line HuH-7 cells as an in vitro system to investigate liver toxicity. Possible synergistic or antagonistic metabolic changes after co-exposure scenarios were investigated. Toxicological data of the water soluble tetrazolium (WST-1) assay for cell proliferation and genotoxicity assessment using the Comet assay were combined with an untargeted as well as a targeted lipidomics approach. We found an attenuated cytotoxicity and an altered metabolic profile in co-exposure experiments with cerium dioxide, indicating an interaction of both compounds at these endpoints. Single exposure against cerium dioxide showed a genotoxic effect in the Comet assay. Conversely, acetaminophen exhibited no genotoxic effect. Comet assay data do not indicate an enhancement of genotoxicity after co-exposure. The results obtained in this study highlight the advantage of investigating co-exposure scenarios, especially for bioactive substances.

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Parametric Optimization of an Air–Liquid Interface System for Flow-Through Inhalation Exposure to Nanoparticles: Assessing Dosimetry and Intracellular Uptake of CeO2 Nanoparticles

Cited by 28 publications

References 82 publications

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

Combinatory Effects of Cerium Dioxide Nanoparticles and Acetaminophen on the Liver—A Case Study of Low-Dose Interactions in Human HuH-7 Cells

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