Reaction between Graphene Oxide and Intracellular Glutathione Affects Cell Viability and Proliferation

ACS Appl Mater Interfaces. 2021 Jan 27;13(3):3528-3535. doi: 10.1021/acsami.0c17523. Epub 2021 Jan 11.


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.

Keywords: cancer cells; carbon nanomaterial; oxidation; reactive oxygen species; reduction.

MeSH terms

  • Biocompatible Materials / metabolism
  • Biocompatible Materials / toxicity*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects*
  • Glutathione / metabolism*
  • Graphite / metabolism
  • Graphite / toxicity*
  • HeLa Cells
  • Humans
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism


  • Biocompatible Materials
  • Reactive Oxygen Species
  • graphene oxide
  • Graphite
  • Glutathione