title: Graphene Oxide Nanoribbons Induce Autophagic Vacuoles in Neuroblastoma Cell Lines.
abstract: Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO) nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs) and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2) and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS), mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM) for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells.
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. emanuela.mari@uniroma1.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mari
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. Stefania.mardente@uniroma1.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mardente
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. emanuela.morgante@uniroma1.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morgante
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. marco.tafani@uniroma1.it.|Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, 00163 Rome, Italy. marco.tafani@uniroma1.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Tafani
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. emanuela.lococo@yahoo.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lococo
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. flavia.fico@unifr.ch.
authors.forename: Flavia
authors.initials: F
authors.lastname: Fico
authors.affiliation: Department of Chemistry, University of Rome Tor Vergata, 00173 Roma, Italy. federicavalentini.chem@gmail.com.
authors.forename: Federica
authors.initials: F
authors.lastname: Valentini
authors.affiliation: Department of Experimental Medicine, University of Rome Sapienza, 00161 Roma, Italy. alessandra.zicari@uniroma1.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zicari
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D006108:Graphite / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D009447:Neuroblastoma / Q000378:metabolism*; D010087:Oxides / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D010087:Oxides; D017382:Reactive Oxygen Species; D006108:Graphite
keywords: autophagy; cytotoxicity; graphene oxide; nanoribbons; neuroblastoma