title: The potentiation effect makes the difference: non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro.
abstract: Here we examined whether the addition of a non-toxic concentration (6.25 μg/mL) of zinc oxide nanoparticles (ZnONPs: 19, 35 and 57 nm, respectively) modulates the cytotoxicity of copper nanoparticles (CuNPs, 63 nm in size) in the human hepatoma cell line HepG2. The cytotoxic effect of CuNPs on HepG2 cells was markedly enhanced by the ZnONPs, the largest ZnONPs causing the highest increase in toxicity. However, CuNPs cytotoxicity was not affected by co-incubation with medium containing only zinc ions, indicating the increase in toxicity might be attributed to the particle form of ZnONPs. Transmission electron microscopy (TEM) revealed the presence of CuNPs and ZnONPs inside the cells co-exposed to both types of NP and outflow of cytoplasm through the damaged cell membrane. Inductively coupled plasma mass spectrometry (ICP-MS) determined an increase in the concentration of zinc and a decrease in that of copper in co-exposed cells. On the basis of these results, we propose that accumulation of large numbers of ZnONPs in the cells alters cellular membranes and the cytotoxicity of CuNPs is increased.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Lingxiangyu
authors.initials: L
authors.lastname: Li
authors.affiliation: Departamento de Medio Ambiente, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid 28040, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Fernández-Cruz
authors.affiliation: Departamento de Medio Ambiente, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid 28040, Spain.
authors.forename: Mona
authors.initials: M
authors.lastname: Connolly
authors.affiliation: Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid 28040, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Conde
authors.affiliation: Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid 28040, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Fernández
authors.affiliation: Department of Chemistry, Technische Universität München, Garching 85747, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schuster
authors.affiliation: Departamento de Medio Ambiente, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid 28040, Spain. Electronic address: jmnavas@inia.es.
authors.forename: José María
authors.initials: JM
authors.lastname: Navas
mesh_terms: D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D066298:In Vitro Techniques; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D003300:Copper; D015034:Zinc Oxide
keywords: CuNPs; Cytotoxicity assays; HepG2; Potentiation effect; ZnONPs