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An in vitro testing strategy towards mimicking the inhalation of high aspect ratio nanoparticles

  • Endes, Carola BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Schmid, Otmar Comprehensive Pneumology Centre, Institute of Lung Biology and Disease, Helmholtz Zentrum Muenchen, Germany
  • Kinnear, Calum BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Mueller, Silvana Polymer Chemistry and Materials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Camarero-Espinosa, Sandra Polymer Chemistry and Materials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Vanhecke, Dimitri BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Foster, E. Johan Polymer Chemistry and Materials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Petri-Fink, Alke BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland - Department of Chemistry, University of Fribourg, Switzerland
  • Rothen-Rutishauser, Barbara BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Weder, Christoph Polymer Chemistry and Materials, Adolphe Merkle Institute, University of Fribourg, Switzerland
  • Clift, Martin J. D. BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Switzerland
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    23.09.2014
Published in:
  • Particle and Fibre Toxicology. - 2015, vol. 11, no. 1, p. 40
High aspect ratio nanoparticles
Air liquid interface
In vitro
Inhalation
Characterisation
Alternative testing strategies
Cellulose nanocrystals
English The challenge remains to reliably mimic human exposure to high aspect ratio nanoparticles (HARN) via inhalation. Sophisticated, multi-cellular in vitro models are a particular advantageous solution to this issue, especially when considering the need to provide realistic and efficient alternatives to invasive animal experimentation for HARN hazard assessment. By incorporating a systematic test-bed of material characterisation techniques, a specific air-liquid cell exposure system with real-time monitoring of the cell-delivered HARN dose in addition to key biochemical endpoints, here we demonstrate a successful approach towards investigation of the hazard of HARN aerosols in vitro.Methods: Cellulose nanocrystals (CNCs) derived from cotton and tunicates, with differing aspect ratios (~9 and ~80), were employed as model HARN samples. Specifically, well-dispersed and characterised CNC suspensions were aerosolised using an “Air Liquid Interface Cell Exposure System” (ALICE) at realistic, cell-delivered concentrations ranging from 0.14 to 1.57 μg/cm2. The biological impact (cytotoxicity, oxidative stress levels and pro-inflammatory effects) of each HARN sample was then assessed using a 3D multi-cellular in vitro model of the human epithelial airway barrier at the air liquid interface (ALI) 24 hours post-exposure. Additionally, the testing strategy was validated using both crystalline quartz (DQ12) as a positive particulate control in the ALICE system and long fibre amosite asbestos (LFA) to confirm the susceptibility of the in vitro model to a fibrous insult.Results: A rapid (≤4 min), controlled nebulisation of CNC suspensions enabled a dose-controlled and spatially homogeneous CNC deposition onto cells cultured under ALI conditions. Real-time monitoring of the cell-delivered CNC dose with a quartz crystal microbalance was accomplished. Independent of CNC aspect ratio, no significant cytotoxicity (p > 0.05), induction of oxidative stress, or (pro)-inflammatory responses were observed up to the highest concentration of 1.57 μg/cm². Both DQ12 and LFA elicited a significant (p < 0.05) pro-inflammatory response at sub-lethal concentrations in vitro.Conclusion: In summary, whilst the present study highlights the benign nature of CNCs, it is the advanced technological and mechanistic approach presented that allows for a state of the art testing strategy to realistically and efficiently determine the in vitro hazard concerning inhalation exposure of HARN.
Faculty
Faculté des sciences et de médecine
Department
Département de Chimie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304214
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