PMID- 33428377 OWN - NLM STAT- MEDLINE DCOM- 20210302 LR - 20210302 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 13 IP - 3 DP - 2021 Jan 27 TI - Reaction between Graphene Oxide and Intracellular Glutathione Affects Cell Viability and Proliferation. PG - 3528-3535 LID - 10.1021/acsami.0c17523 [doi] AB - Graphene oxide (GO) is currently developed for biomedical applications as a promising nanoplatform for drug delivery, phototherapy, and biosensing. As a consequence, its safety and cytotoxicity issues have attracted extensive attention. It has been demonstrated that GO causes an increase of intracellular oxidative stress, likely leading to its cytotoxicity and inhibition of cell proliferation. Being one of the main reductive intracellular substances, glutathione (GSH) is vital in the regulation of the oxidative stress level to maintain normal cellular functions. In this study, we found that GSH could be oxidized to GSSG by GO, leading to the formation of reduced GO (rGO). GSH depletion affects the intracellular reductive/oxidative balance, provoking the increase of the reactive oxygen species level, sequentially inhibiting cell viability and proliferation. Therefore, the reaction between GO and GSH provides a new perspective to explain the origin of GO cytotoxicity. FAU - Ma, Baojin AU - Ma B AD - CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS, Strasbourg 67000, France. FAU - Guo, Shi AU - Guo S AD - CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS, Strasbourg 67000, France. FAU - Nishina, Yuta AU - Nishina Y AUID- ORCID: 0000-0002-4958-1753 AD - Graduate School of Natural Science and Technology, Okayama University, Tsushimanaka, Kita-ku, Okayama 700-8530, Japan. AD - Research Core for Interdisciplinary Sciences, Okayama University, Tsushimanaka, Kita-ku, Okayama 700-8530, Japan. FAU - Bianco, Alberto AU - Bianco A AUID- ORCID: 0000-0002-1090-296X AD - CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS, Strasbourg 67000, France. LA - eng PT - Journal Article DEP - 20210111 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Biocompatible Materials) RN - 0 (Reactive Oxygen Species) RN - 0 (graphene oxide) RN - 7782-42-5 (Graphite) RN - GAN16C9B8O (Glutathione) SB - IM MH - Biocompatible Materials/metabolism/*toxicity MH - Cell Line MH - Cell Proliferation/drug effects MH - Cell Survival/*drug effects MH - Glutathione/*metabolism MH - Graphite/metabolism/*toxicity MH - HeLa Cells MH - Humans MH - Oxidative Stress/*drug effects MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - cancer cells OT - carbon nanomaterial OT - oxidation OT - reactive oxygen species OT - reduction EDAT- 2021/01/12 06:00 MHDA- 2021/03/03 06:00 CRDT- 2021/01/11 17:09 PHST- 2021/01/12 06:00 [pubmed] PHST- 2021/03/03 06:00 [medline] PHST- 2021/01/11 17:09 [entrez] AID - 10.1021/acsami.0c17523 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2021 Jan 27;13(3):3528-3535. doi: 10.1021/acsami.0c17523. Epub 2021 Jan 11.