In vitro and in vivo comparison of the immunotoxicity of single- and multi-layered graphene oxides with or without pluronic F-127

• Published in: Scientific reports 2016-12, Vol.6 (1), p.38884, Article 38884
• Main Authors: Cho, Young Chol, Pak, Pyo June, Joo, Yong Hoon, Lee, Hoi-Seon, Chung, Namhyun
• Format: Article
• Language: English
• Subjects: 13/21; 13/31; 14/3; 14/34; 631/154/570; 631/92/1933; 82/51; Animals; Apoptosis; Apoptosis - drug effects; Biocompatibility; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Cytochalasin D - pharmacology; Dose-Response Relationship, Drug; Drug delivery; Graphite - toxicity; Humanities and Social Sciences; Humans; IL-1β; Immunotoxicity; Injection; Interleukin-1beta - biosynthesis; Intravenous administration; Kidney - drug effects; Kidney - immunology; Kidneys; L-Lactate Dehydrogenase - analysis; Lung - drug effects; Lung - immunology; Lungs; Mice; multidisciplinary; Necrosis; Oxides; Oxides - toxicity; Phagocytosis; Phagocytosis - drug effects; Poloxamer - toxicity; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Tetradecanoylphorbol Acetate - pharmacology; THP-1 Cells; Toxicity; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38884

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.