title: In vitro evaluation of graphene oxide nanosheets on immune function.
abstract: OBJECTIVE
  Graphene oxide (GO) has attracted the scientific community attention due to its novel properties and wide range of potential applications including hyperthermia cancer therapy. However, little is known about the GO effects on the immune function which involves both innate and adaptive defence mechanisms through the activation of different cell populations and secretion of several cytokines. The effect of different GO nanosheets designed for hyperthermia cancer therapy on macrophage and lymphocyte function should be determined before using GO for this application.
  
  
  METHODS
  The effects of GO nanosheets with 1 (1-GOs) and 6 arms (6-GOs) of polyethylene glycol on RAW-264.7 macrophages and primary splenocytes (as approximation to the in vivo situation) were evaluated through the proinflammatory cytokine secretion and the modulation of cell proliferation in the presence of specific stimuli for either T-lymphocytes (concanavalin A, anti-CD3 antibody) or B-lymphocytes/macrophages (lipopolysaccharide).
  
  
  RESULTS
  6-GOs significantly increased the secretion of TNF-α by RAW-264.7 macrophages without alteration of IL-6 and IL-1β levels. The treatment of primary splenocytes with 1-GOs and 6-GOs in the presence of concanavalin A, anti-CD3 antibody and lipopolysaccharide, produced significant dose-dependent decreases of cell proliferation and IL-6 levels, revealing weak inflammatory properties of GOs which are favourable for hyperthermia cancer therapy.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: mjfeito@pdi.ucm.es.
authors.forename: M J
authors.initials: MJ
authors.lastname: Feito
authors.affiliation: Department of Inorganic and Bioinorganic Chemistry, Faculty of Pharmacy, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain; TEMA-NRD, Mechanical Engineering Department and Aveiro Institute of Nanotechnology (AIN), University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: mvila@farm.ucm.es.
authors.forename: M
authors.initials: M
authors.lastname: Vila
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: conchitamatesanz@hotmail.com.
authors.forename: M C
authors.initials: MC
authors.lastname: Matesanz
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: javilinares_88@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Linares
authors.affiliation: TEMA-NRD, Mechanical Engineering Department and Aveiro Institute of Nanotechnology (AIN), University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: ggoncalves@ua.pt.
authors.forename: G
authors.initials: G
authors.lastname: Gonçalves
authors.affiliation: TEMA-NRD, Mechanical Engineering Department and Aveiro Institute of Nanotechnology (AIN), University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: paulam@ua.pt.
authors.forename: P A A P
authors.initials: PA
authors.lastname: Marques
authors.affiliation: Department of Inorganic and Bioinorganic Chemistry, Faculty of Pharmacy, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, 28040 Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain. Electronic address: vallet@farm.ucm.es.
authors.forename: M
authors.initials: M
authors.lastname: Vallet-Regí
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid, Spain. Electronic address: jmrojo@cib.csic.es.
authors.forename: J M
authors.initials: JM
authors.lastname: Rojo
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, 28040 Madrid, Spain. Electronic address: portoles@quim.ucm.es.
authors.forename: M T
authors.initials: MT
authors.lastname: Portolés
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D006108:Graphite
keywords: Biocompatibility; Cytokine; Graphene oxide; Lymphocyte; Macrophage