title: In vitro cytotoxicity evaluation of graphene oxide from the peroxidase-like activity perspective.
abstract: In this study, PEGylated graphene oxide (PEG-GO)-hemin composite structure was constructed. Hemin in the form of nanoscaled aggregates were immobilized on PEG-GO sheets by the π-π stacking super-molecular interaction. Via catalyzing the oxidation of chromogenic substrates, we elicited the obtained PEG-GO-Hemin composite sheets have much higher peroxidase-like activity compared to hemin or PEG-GO alone, which is due to the introduction of enzyme active center of hemin with high dispersity, the excellent affinity to organic substrate through π-π stacking and/or electrostatic adsorption and the rapid electron transfer capability of PEG-GO. Similarly, PEG-GO-Hemin was found to be able to catalyze the oxidation of low density lipoprotein (LDL) by H2O2, resulting in toxicity to porcine iliac endothelial cells (PIECs) in vitro. Furthermore, we also demonstrated that PEG-GO sheets showed enhanced peroxidase activity when met hemin containing proteins including hemoglobin and cytochrome c. High glucose level (HG) in human umbilical vein endothelial cells (HUVECs) can induce cytochrome c to release from the respiratory chain, thus applying PEG-GO under HG condition could cause a much higher peroxidase-like activity, resulting in the production of hydroxyl radical (OH) and cytochrome c radical (cytochrome c), which eventually enhance the apoptosis. These results suggest GO has potential hazard for biomedical applications in some pathophysiological conditions.
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Patent Examination Cooperation Jiangsu Centre of the Patent Office, SIPO, Suzhou 215163, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, PR China; College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210000, PR China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Lou
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.affiliation: Research Centre of Clinical Oncology, Jiangsu Cancer Hospital, Nanjing 210009, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, PR China. Electronic address: guning@seu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, PR China. Electronic address: zhangyu@seu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002384:Catalysis; D020134:Catalytic Domain; D045304:Cytochromes c / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D005947:Glucose / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D006427:Hemin / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000737:chemistry; D018384:Oxidative Stress; D010087:Oxides / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010544:Peroxidases / Q000737:chemistry*; D055672:Static Electricity; D013379:Substrate Specificity; D013552:Swine
chemical_list: D008077:Lipoproteins, LDL; D010087:Oxides; D006427:Hemin; D006108:Graphite; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D010544:Peroxidases; D005947:Glucose; D010100:Oxygen
keywords: Cytotoxicity; Graphene oxide; Hemin; Peroxidase mimics; Reactive oxygen species