PMID- 30239936 OWN - NLM STAT- MEDLINE DCOM- 20191219 LR - 20191219 IS - 1096-0929 (Electronic) IS - 1096-0929 (Linking) VI - 167 IP - 1 DP - 2019 Jan 1 TI - Systematic Assessment of the Toxicity and Potential Mechanism of Graphene Derivatives In Vitro and In Vivo. PG - 269-281 LID - 10.1093/toxsci/kfy235 [doi] AB - Graphene is a two-dimensional crystal that is stripped from pristine graphite and made of single layer of carbon atoms. Containing numerous functional groups, graphene derivatives (GDs) could be easily modified and have aroused great attention for potential applications in biomedicine. However, pristine graphene and graphene oxide (GO) could arouse cell and animal toxicity. To screen GDs with high biocompatibility applied for biomedicine, general comparison was performed about the toxicities of six GDs with diverse types of surface modification, size, and redox state, including GO, reduced GO (rGO), graphene quantum dot (GQD), aminated GQD (GQD-NH2), carboxyl GQD (GQD-COOH), and graphene oxide quantum dot (GOQD). In contrast, it was found that large particle size, oxidation state, high concentration, and long exposure time were unfavorable factors affecting the cell viability. We further explored the mechanism of different toxicity, which could be contribute to cell membrane destruction by sharpened edges of GDs (LDH release, hemolysis), ROS production, immuno-inflammatory responses, and activation of apoptotic pathways (IKK/IkappaBalpha/NF-kappaB and BAX/BCL-2). Overall, our combined data primarily explored the related biochemical and molecular mechanism underlying the biological behaviors and toxicity of GDs, and we also identified GQD, GQD-NH2, GQD-COOH, and GOQD could be safely used for biomedical application as drug carriers. FAU - Li, Jian AU - Li J AD - Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Zhang, Xizhi AU - Zhang X AD - College of Biology, Hunan University, Changsha, Hunan 410082, China. FAU - Jiang, Jing AU - Jiang J AD - Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Wang, Yanjie AU - Wang Y AD - Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Jiang, Haiye AU - Jiang H AD - Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Zhang, Junhua AU - Zhang J AD - Department of Blood Transfusion of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Nie, Xinmin AU - Nie X AD - Department of Clinical Laboratory of the Third Xiangya Hospital, Central South University, Hunan 410013, China. FAU - Liu, Bin AU - Liu B AD - College of Biology, Hunan University, Changsha, Hunan 410082, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Biocompatible Materials) RN - 0 (Drug Carriers) RN - 0 (Reactive Oxygen Species) RN - 0 (graphene oxide) RN - 7782-42-5 (Graphite) SB - IM MH - Amination MH - Apoptosis/drug effects MH - Biocompatible Materials/chemistry/*toxicity MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Drug Carriers/chemistry/*toxicity MH - Graphite/chemistry/*toxicity MH - Hepatocytes/*drug effects/metabolism MH - Humans MH - Oxidation-Reduction MH - Particle Size MH - Quantum Dots/chemistry/*toxicity MH - Reactive Oxygen Species/metabolism MH - Surface Properties EDAT- 2018/09/22 06:00 MHDA- 2019/12/20 06:00 CRDT- 2018/09/22 06:00 PHST- 2018/09/22 06:00 [pubmed] PHST- 2019/12/20 06:00 [medline] PHST- 2018/09/22 06:00 [entrez] AID - 5098225 [pii] AID - 10.1093/toxsci/kfy235 [doi] PST - ppublish SO - Toxicol Sci. 2019 Jan 1;167(1):269-281. doi: 10.1093/toxsci/kfy235.