Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines

Research output: Contribution to journalArticle

Authors

  • Iris Hansjosten
  • Juliane Rapp
  • Luisa Reiner
  • Ruben Vatter
  • Susanne Fritsch-Decker
  • Ravindra Peravali
  • Taina Palosaari
  • Elisabeth Joossens
  • Kirsten Gerloff
  • Peter Macko
  • Maurice Whelan
  • Douglas Gilliland
  • Isaac Ojea-Jimenez
  • Marco P Monopoli
  • Louise Rocks
  • David Garry
  • Kenneth Dawson
  • Peter J F Röttgermann
  • Alexandra Murschhauser
  • Joachim O Rädler
  • Selina V Y Tang
  • Pete Gooden
  • Marie-France A Belinga-Desaunay
  • Eva Valsami-Jones
  • Silvia Diabaté
  • Carsten Weiss

External organisations

  • Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
  • European Commission, Joint Research Centre (JRC), Via E. Fermi 2749, 21027, Ispra (VA), Italy.
  • Centre for BioNano Interactions (CBNI), School of Chemistry and Chemical Biology, University College Dublin (UCD), Belfield, Dublin 4, Ireland.
  • Faculty of Physics and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München (LMU), Geschwister-Scholl-Platz 1, 80539, Munich, Germany.
  • Promethean Particles Ltd, 1-3 Genesis Park, Midland Way, Nottingham, NG7 3EF, UK.
  • School of Geography Earth and Environmental Sciences (GEES), University of Birmingham (UoB), Edgbaston, Birmingham, B15 2TT, UK.

Abstract

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical-chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were toxic in all cell types. TiO2and SiO2MNMs also triggered toxicity in some, but not all, cell types and the cell type-specific effects were influenced by the specific coating and surface modification. CeO2MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type-specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.

Details

Original languageEnglish
Pages (from-to)633-649
Number of pages17
JournalArchives of toxicology
Volume92
Issue number2
Early online date8 Nov 2017
Publication statusPublished - 1 Feb 2018

Keywords

  • Journal Article, maufactured nanomaterials , toxicity , high-throughput screening , cell type specificity , cell death , adverse outcome pathways , nanosafety