title: In vitro and in vivo comparison of the immunotoxicity of single- and multi-layered graphene oxides with or without pluronic F-127.
abstract: Graphene oxide (GO) has been a focus of research in the fields of electronics, energy, and biomedicine, including drug delivery. Thus, single- and multi-layered GO (SLGO and MLGO) have been produced and investigated. However, little information on their toxicity and biocompatibility is available. In the present study, we performed a comprehensive study of the size- and dose-dependent toxicity of GOs in the presence or absence of Pluronic F-127 on THP-1 cells by examining their viability, membrane integrity, levels of cytokine and ROS production, phagocytosis, and cytometric apoptosis. Moreover, as an extended study, a toxicity evaluation in the acute and chronic phases was performed in mice via intravenous injection of the materials. GOs exhibited dose- and size-dependent toxicity. Interestingly, SLGO induced ROS production to a lesser extent than MLGO. Cytometric analysis indicated that SLGO induced necrosis and apoptosis to a lesser degree than MLGO. In addition, cell damage and IL-1β production were influenced by phagocytosis. A histological animal study revealed that GOs of various sizes induced acute and chronic damage to the lung and kidney in the presence or absence of Pluronic F-127. These results will facilitate studies of GO prior to its biomedical application.
authors.affiliation: Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Young Chol
authors.initials: YC
authors.lastname: Cho
authors.affiliation: Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Pyo June
authors.initials: PJ
authors.lastname: Pak
authors.affiliation: Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Joo
authors.affiliation: College of Agriculture and Life Science, Chonbuk National University, Jeonju 54907, Korea.
authors.forename: Hoi-Seon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Namhyun
authors.initials: N
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D015638:Cytochalasin D / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects* / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009336:Necrosis; D010087:Oxides / Q000633:toxicity; D010587:Phagocytosis / Q000187:drug effects; D020442:Poloxamer / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000074084:THP-1 Cells; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D010087:Oxides; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D020442:Poloxamer; D015638:Cytochalasin D; D006108:Graphite; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate