title: Interaction of gold nanoparticles and nickel(II) sulfate affects dendritic cell maturation.
abstract: Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulfate (NiSO4) and GNPs on the maturation response of dendritic cells (DCs) was explored. Exposure to GNPs or NiSO4separately induced cell activation. When cells were exposed to a mixture of both, however, the observed cell activation pattern indicated a competitive rather than an additive effect of both inducers with levels similar to those induced by NiSO4alone. Quantification of the GNP uptake by DCs demonstrated a significant decrease in intracellular gold content during co-incubation with NiSO4. An extensive physiochemical characterization was performed to determine the interaction between GNPs and NiSO4in the complex physiological media using nanoparticle tracking analyses, disc centrifugation, UV-visible spectroscopy, ICP-MS analyses, zeta potential measurements, electron microscopy, and proteomics. Although GNPs and NiSO4did not directly interact with each other, the presence of NiSO4in the physiological media resulted in changes in GNPs' charge and their associated protein corona (content and composition), which may contribute to a decreased cellular uptake of GNPs and sustaining the nickel-induced DC maturation. The presented results provide new insights in the interaction of heavy metals and NPs in complex physiological media. Moreover, this study highlights the necessity of mixture toxicology, since these combined exposures are highly relevant for human subjection to NPs and risk assessment of nanomaterials.
authors.affiliation: a Health Unit , Flemish Institute for Technological Research , Mol , Belgium.|b Biomedical Research Institute, Hasselt University , Diepenbeek , Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Deville
authors.affiliation: a Health Unit , Flemish Institute for Technological Research , Mol , Belgium.|c Lung Toxicology, Catholic University Leuven , Leuven , Belgium.
authors.forename: Birgit
authors.initials: B
authors.lastname: Baré
authors.affiliation: d Inorganic Nanoparticles Group, Institut Català de Nanotecnologia, Campus UAB , Bellaterra , Spain.|e Universitat Autònoma de Barcelona, Campus UAB , Bellaterra , Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Piella
authors.affiliation: a Health Unit , Flemish Institute for Technological Research , Mol , Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Tirez
authors.affiliation: c Lung Toxicology, Catholic University Leuven , Leuven , Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoet
authors.affiliation: f Centre for BioNano Interactions, School of Chemistry and Chemical Biology, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin , Belfield , Dublin , Ireland.
authors.forename: Marco P
authors.initials: MP
authors.lastname: Monopoli
authors.affiliation: f Centre for BioNano Interactions, School of Chemistry and Chemical Biology, UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin , Belfield , Dublin , Ireland.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.affiliation: d Inorganic Nanoparticles Group, Institut Català de Nanotecnologia, Campus UAB , Bellaterra , Spain.|g Vall d'Hebron Institute of Research , Barcelona , Spain , and.|h Institució Catalana de Recerca i Estudis Avançats , Barcelona , Spain.
authors.forename: Victor F
authors.initials: VF
authors.lastname: Puntes
authors.affiliation: a Health Unit , Flemish Institute for Technological Research , Mol , Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Nelissen
mesh_terms: D000954:Antigens, Surface / Q000235:genetics; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004347:Drug Interactions; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006046:Gold / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009532:Nickel / Q000737:chemistry / Q000633:toxicity*; D000066970:Protein Corona / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000954:Antigens, Surface; D000066970:Protein Corona; C029938:nickel sulfate; D006046:Gold; D009532:Nickel
keywords: Co-exposure; dendritic cells; gold nanoparticles; nickel sulfate