Assessment of Carbon Nanotubes on Barrier Function, Ciliary Beating Frequency and Cytokine Release in In Vitro Models of the Respiratory Tract

The exposure to inhaled carbon nanotubes (CNT) may have adverse effects on workers upon chronic exposure. In order to assess the toxicity of inhaled nanoparticles in a physiologically relevant manner, an air–liquid interface culture of mono and cocultures of respiratory cells and assessment in reconstructed bronchial and alveolar tissues was used. The effect of CNT4003 reference particles applied in simulated lung fluid was studied in bronchial (Calu-3 cells, EpiAirway™ and MucilAir™ tissues) and alveolar (A549 +/−THP-1 and EpiAlveolar™ +/−THP-1) models. Cytotoxicity, transepithelial electrical resistance, interleukin 6 and 8 secretion, mucociliary clearance and ciliary beating frequency were used as readout parameters. With the exception of increased secretion of interleukin 6 in the EpiAlveolar™ tissues, no adverse effects of CNT4003 particles, applied at doses corresponding to the maximum estimated lifetime exposure of workers, in the bronchial and alveolar models were noted, suggesting no marked differences between the models. Since the doses for whole-life exposure were applied over a shorter time, it is not clear if the interleukin 6 increase in the EpiAlveolar™ tissues has physiological relevance.

[1]  S. Frentzel,et al.  Ciliary Beat Frequency: Proceedings and Recommendations from a Multi-laboratory Ring Trial Using 3-D Reconstituted Human Airway Epithelium to Model Mucociliary Clearance , 2022, Alternatives to laboratory animals : ATLA.

[2]  A. Nasibulin,et al.  In vitro toxicity of carbon nanotubes: a systematic review , 2022, RSC advances.

[3]  J. Ruíz-Cabello,et al.  Delayed alveolar clearance of nanoparticles through control of coating composition and interaction with lung surfactant protein A. , 2021, Materials Science and Engineering C: Materials for Biological Applications.

[4]  A. Lansley,et al.  Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro. , 2021, Regulatory toxicology and pharmacology : RTP.

[5]  A. T. Saber,et al.  In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT , 2021, Particle and fibre toxicology.

[6]  U. Vogel,et al.  In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT , 2021, Particle and Fibre Toxicology.

[7]  E. Fröhlich,et al.  Screening for Effects of Inhaled Nanoparticles in Cell Culture Models for Prolonged Exposure , 2021, Nanomaterials.

[8]  Bhupinder Singh,et al.  Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention , 2021, Journal of Nanobiotechnology.

[9]  G. Phillips,et al.  Acute electronic vapour product whole aerosol exposure of 3D human bronchial tissue results in minimal cellular and transcriptomic responses when compared to cigarette smoke , 2021, Toxicology Research and Application.

[10]  B. Cummings,et al.  Safe Nanoparticles: Are We There Yet? , 2020, International journal of molecular sciences.

[11]  D. Kirkpatrick,et al.  Evaluation of nafamostat mesylate safety and inhibition of SARS-CoV-2 replication using a 3-dimensional human airway epithelia model , 2020, bioRxiv.

[12]  Yulong Chen,et al.  Mechanisms of the lipopolysaccharide-induced inflammatory response in alveolar epithelial cell/macrophage co-culture , 2020, Experimental and therapeutic medicine.

[13]  David M. Brown,et al.  Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multi-Walled Carbon Nanotubes. , 2020, ACS nano.

[14]  Sebastian F Salathe,et al.  Losartan Rescues Inflammation-Related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis. , 2020, American journal of respiratory and critical care medicine.

[15]  T. Cedervall,et al.  Understanding the Lipid and Protein Corona Formation on Different Sized Polymeric Nanoparticles , 2020, Scientific Reports.

[16]  T. Walles,et al.  Investigation on Ciliary Functionality of Different Airway Epithelial Cell Lines in Three-Dimensional Cell Culture , 2019, Tissue engineering. Part A.

[17]  J. Tuszynski,et al.  Tubulin: Structure, Functions and Roles in Disease , 2019, Cells.

[18]  T. Orsière,et al.  Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model , 2019, Nanomaterials.

[19]  Song Huang,et al.  In vitro safety and performance evaluation of a seawater solution enriched with copper, hyaluronic acid, and eucalyptus for nasal lavage , 2019, Medical devices.

[20]  E. Fröhlich,et al.  Air-liquid interface culture changes surface properties of A549 cells. , 2019, Toxicology in vitro : an international journal published in association with BIBRA.

[21]  D. Greco,et al.  Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model , 2019, ACS nano.

[22]  P. Wick,et al.  Acute effects of multi-walled carbon nanotubes on primary bronchial epithelial cells from COPD patients , 2018, Nanotoxicology.

[23]  C. Lehr,et al.  Combining MucilAir™ and Vitrocell® Powder Chamber for the In Vitro Evaluation of Nasal Ointments in the Context of Aerosolized Pollen , 2018, Pharmaceutics.

[24]  P. Wick,et al.  Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells. , 2017, ACS nano.

[25]  FieldsWanda,et al.  Characterization and Application of the VITROCELL VC1 Smoke Exposure System and 3D EpiAirway Models for Toxicological and e-Cigarette Evaluations , 2017 .

[26]  E. Fröhlich.  Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening , 2017, Drug delivery.

[27]  Eleonore Fröhlich,et al.  Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds , 2016, Front. Pharmacol..

[28]  Ivan Rusyn,et al.  Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution , 2016, Inhalation toxicology.

[29]  M. Larramendy,et al.  Nanomaterials - Toxicity and Risk Assessment , 2015 .

[30]  E. Fröhlich,et al.  In Vitro Assessment of Chronic Nanoparticle Effects on Respiratory Cells , 2015 .

[31]  I. Yu,et al.  Three-Day Continuous Exposure Monitoring of CNT Manufacturing Workplaces , 2015, BioMed research international.

[32]  M. Kreft,et al.  The characterization of the human cell line Calu-3 under different culture conditions and its use as an optimized in vitro model to investigate bronchial epithelial function. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[33]  S. Vranic,et al.  Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[34]  N. Cohen,et al.  The Effect of Drugs and Other Compounds on the Ciliary Beat Frequency of Human Respiratory Epithelium , 2014, American Journal of Rhinology & Allergy.

[35]  Robert Landsiedel,et al.  In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[36]  L. Rasmussen,et al.  Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. , 2012, Mutagenesis.

[37]  K. Inaba,et al.  Tubulin-dynein system in flagellar and ciliary movement , 2012, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[38]  D. Daines,et al.  Characterization of extended co-culture of non-typeable Haemophilus influenzae with primary human respiratory tissues , 2012, Experimental biology and medicine.

[39]  D. Dix,et al.  Informing Selection of Nanomaterial Concentrations for ToxCast in Vitro Testing Based on Occupational Exposure Potential , 2011, Environmental health perspectives.

[40]  H. Smyth,et al.  Controlled Pulmonary Drug Delivery , 2011 .

[41]  G. Bae,et al.  Exposure assessment of carbon nanotube manufacturing workplaces , 2010, Inhalation toxicology.

[42]  Y. Fujitani,et al.  Generation of Airborne Multi-Walled Carbon Nanotubes for Inhalation Studies , 2009 .

[43]  J. Mauderly,et al.  RESPONSES OF DIFFERENTIATED PRIMARY HUMAN LUNG EPITHELIAL CELLS TO EXPOSURE TO DIESEL EXHAUST AT AN AIR-LIQUID INTERFACE , 2007, Experimental lung research.

[44]  Ben Forbes,et al.  Culture of Calu-3 Cells at the Air Interface Provides a Representative Model of the Airway Epithelial Barrier , 2006, Pharmaceutical Research.

[45]  M. Sanderson,et al.  Ciliary beat frequency is maintained at a maximal rate in the small airways of mouse lung slices. , 2006, American journal of respiratory cell and molecular biology.

[46]  H. Mori,et al.  ATP regulation of ciliary beat frequency in rat tracheal and distal airway epithelium , 2005, Experimental physiology.

[47]  A. Collins,et al.  Genotoxic effects of asbestos in humans. , 2004, Mutation research.

[48]  A. Tonks,et al.  Dipalmitoylphosphatidylcholine modulates inflammatory functions of monocytic cells independently of mitogen activated protein kinases , 2001, Clinical and experimental immunology.

[49]  V. Nicolas,et al.  Surface-Modified Biodegradable Nanoparticles' Impact on Cytotoxicity and Inflammation Response on a Co-Culture of Lung Epithelial Cells and Human-Like Macrophages. , 2016, Journal of biomedical nanotechnology.

[50]  O. Heidi,et al.  The JRC Nanomaterials Repository - Safe handling of nanomaterials in the sub-sampling facility , 2016 .

[51]  Cotogno Giulio,et al.  Multi-walled Carbon Nanotubes, NM-400, NM-401, NM-402, NM-403: Characterisation and Physico-Chemical Properties , 2014 .

[52]  C. Ehrhardt,et al.  In Vitro Cell Culture Models for Evaluating Controlled Release Pulmonary Drug Delivery , 2011 .