title: Endoperoxides Revealed as Origin of the Toxicity of Graphene Oxide.
abstract: Potential biomedicinal applications of graphene oxide (GO), for example, as a carrier of biomolecules or a reagent for photothermal therapy and biosensing, are limited by its cytotoxicity and mutagenicity. It is believed that these properties are at least partially caused by GO-induced oxidative stress in cells. However, it is not known which chemical fragments of GO are responsible for this unfavorable effect. We generated four GOs containing variable redox-active groups on the surface, including Mn(2+), C-centered radicals, and endoperoxides (EPs). A comparison of the abilities of these materials to generate reactive oxygen species in human cervical cancer cells revealed that EPs play a crucial role in GO-induced oxidative stress. These data could be applied to the rational design of biocompatible nontoxic GOs for biomedical applications.
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, 91054 Erlangen (Germany).
authors.forename: Hanna
authors.initials: H
authors.lastname: Pieper
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, 91054 Erlangen (Germany).
authors.forename: Serghei
authors.initials: S
authors.lastname: Chercheja
authors.affiliation: FAU, Department of Chemistry and Pharmacy and Institute of Advanced Materials and Processes (ZMP), Dr.-Mack-Str. 81, 90762 Fürth (Germany).
authors.forename: Siegfried
authors.initials: S
authors.lastname: Eigler
authors.affiliation: FAU, Department of Chemistry and Pharmacy and Institute of Advanced Materials and Processes (ZMP), Dr.-Mack-Str. 81, 90762 Fürth (Germany).
authors.forename: Christian E
authors.initials: CE
authors.lastname: Halbig
authors.affiliation: FAU, Department of Chemistry and Pharmacy, Bioinorganic Chemistry, Egerlandstr. 1, 91058 Erlangen (Germany).
authors.forename: Milos R
authors.initials: MR
authors.lastname: Filipovic
authors.affiliation: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, 91054 Erlangen (Germany). andriy.mokhir@fau.de.
authors.forename: Andriy
authors.initials: A
authors.lastname: Mokhir
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D015195:Drug Design; D005260:Female; D006108:Graphite / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D010087:Oxides; D010545:Peroxides; D017382:Reactive Oxygen Species; D006108:Graphite
keywords: endoperoxide; graphene oxides; oxidative stress; reactive oxygen species; toxicity