title: Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells.
abstract: The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most frequently utilized nanomaterials in consumer products; therefore, a comprehensive understanding of their toxicity is necessary. In particular, information about the cellular uptake and size dependence of AgNPs is insufficient. In this study, we evaluated the size-dependent effects of AgNPs by treating the human LoVo cell line, an intestinal epithelium model, with spherical AgNPs of well-defined sizes (10, 20, 40, 60 and 100nm). The cellular uptake was visualized by confocal laser scanning microscopy, and various cytotoxicity parameters were analyzed in a size- and dose-dependent manner. In addition, the cellular proteomic response to 20 and 100nm AgNPs was investigated to increase the understanding of potential mechanisms of action. Our data indicated that cellular uptake and toxicity were regulated by size; smaller particles easily penetrated the cells, and 100nm particles did not. It was hypothesized that this size-dependent effect resulted from the stimulation of a signaling cascade that generated ROS and inflammatory markers, leading to mitochondrial dysfunction and subsequently inducing apoptosis. By contrast, the cell proliferation, was independent of AgNPs particle size, indicating a differentially regulated, ROS-independent pathway.
authors.affiliation: Biotechnology, University of Applied Science, Flensburg, Germany. Electronic address: rona.graff@fh-flensburg.de.
authors.forename: Rona
authors.initials: R
authors.lastname: Miethling-Graff
authors.affiliation: Biotechnology, University of Applied Science, Flensburg, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Rumpker
authors.affiliation: Biotechnology, University of Applied Science, Flensburg, Germany.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Richter
authors.affiliation: Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Thiago
authors.initials: T
authors.lastname: Verano-Braga
authors.affiliation: Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Kjeldsen
authors.affiliation: MEMPHYS Center for Biomembrane Physics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brewer
authors.affiliation: Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark.
authors.forename: James
authors.initials: J
authors.lastname: Hoyland
authors.affiliation: Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark.
authors.forename: Horst-Günter
authors.initials: HG
authors.lastname: Rubahn
authors.affiliation: Biotechnology, University of Applied Science, Flensburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Erdmann
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D012834:Silver
keywords: Cellular uptake; Cytotoxicity; LoVo cell line; Silver nanoparticles