title: Changes in Caco-2 cells transcriptome profiles upon exposure to gold nanoparticles.
abstract: Higher efficacy and safety of nano gold therapeutics require examination of cellular responses to gold nanoparticles (AuNPs). In this work we compared cellular uptake, cytotoxicity and RNA expression patterns induced in Caco-2 cells exposed to AuNP (5 and 30nm). Cellular internalization was dose and time-dependent for both AuNPs. The toxicity was observed by colony forming efficiency (CFE) and not by Trypan blue assay, and exclusively for 5nm AuNPs, starting at the concentration of 200μM (24 and 72h of exposure). The most pronounced changes in gene expression (Agilent microarrays) were detected at 72h (300μM) of exposure to AuNPs (5nm). The biological processes affected by smaller AuNPs were: RNA/zinc ion/transition metal ion binding (decreased), cadmium/copper ion binding and glutathione metabolism (increased). Some Nrf2 responsive genes (several metallothioneins, HMOX, G6PD, OSGIN1 and GPX2) were highly up regulated. Members of the selenoproteins were also differentially expressed. Our findings indicate that exposure to high concentration of AuNPs (5nm) induces metal exposure, oxidative stress signaling pathways, and might influence selenium homeostasis. Some of detected cellular responses might be explored as potential enhancers of anti-cancer properties of AuNPs based nanomedicines.
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: edyta.bajak@ec.europa.eu.
authors.forename: Edyta
authors.initials: E
authors.lastname: Bajak
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy; Department of Clinical and Experimental Medicine, University of Insubria, via J. Dunant, 5, 21100 Varese, Italy. Electronic address: marco.fabbri@uninsubria.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Fabbri
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: jessica.ponti@ec.europa.eu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponti
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: sabrina.gioria@ec.europa.eu.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gioria
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: isaac.ojea-jimenez@ec.europa.eu.
authors.forename: Isaac
authors.initials: I
authors.lastname: Ojea-Jiménez
authors.affiliation: European Commission, JRC, IHCP, Molecular Biology and Genomics (MBG) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: angelo.collotta@ec.europa.eu.
authors.forename: Angelo
authors.initials: A
authors.lastname: Collotta
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: valentina.mariani@gmail.com.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mariani
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: douglas.gillland@ec.europa.eu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gilliland
authors.affiliation: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Nanobiosciences (NBS) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: francois.rossi@jrc.ec.europa.eu.
authors.forename: François
authors.initials: F
authors.lastname: Rossi
authors.affiliation: European Commission, JRC, IHCP, Chemical Assessment and Testing (CAT) Unit, via E. Fermi 2749, 21027 Ispra (VA), Italy. Electronic address: laura.gribaldo@ec.europa.eu.
authors.forename: Laura
authors.initials: L
authors.lastname: Gribaldo
mesh_terms: D018938:Caco-2 Cells / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006046:Gold / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D046228:Microarray Analysis; D053758:Nanoparticles / Q000378:metabolism / Q000633:toxicity*; D010316:Particle Size; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D006046:Gold
keywords: AuNPs uptake; Cellular signaling; Stress responses; Transcriptomics; qPCR