title: Widespread nanoparticle-assay interference: implications for nanotoxicity testing.
abstract: The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Ong
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Chemistry and Biochemistry, Mount Allison University, Sackville, New Brunswick, Canada.
authors.forename: Tyson J
authors.initials: TJ
authors.lastname: MacCormack
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rhett J
authors.initials: RJ
authors.lastname: Clark
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: James D
authors.initials: JD
authors.lastname: Ede
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Van A
authors.initials: VA
authors.lastname: Ortega
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lindsey C
authors.initials: LC
authors.lastname: Felix
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael K M
authors.initials: MK
authors.lastname: Dang
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Guibin
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada; National Institute of Nanotechnology, Edmonton, Alberta, Canada.
authors.forename: Hicham
authors.initials: H
authors.lastname: Fenniri
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jonathan G C
authors.initials: JG
authors.lastname: Veinot
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Greg G
authors.initials: GG
authors.lastname: Goss
mesh_terms: D001681:Biological Assay / Q000592:standards; D006801:Humans; D053758:Nanoparticles / Q000009:adverse effects* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size