Large graphene quantum dots alleviate immune-mediated liver damage

ACS Nano. 2014 Dec 23;8(12):12098-109. doi: 10.1021/nn502466z. Epub 2014 Dec 3.


We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-γ, and a decrease in IFN-γ serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-γ and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-γ production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect.

Keywords: apoptosis; autophagy; graphene; hepatitis; quantum dot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biological Transport
  • Biomarkers / metabolism
  • Cell Line
  • Concanavalin A / adverse effects
  • Cytoprotection / drug effects
  • Gene Expression Regulation / drug effects
  • Graphite / chemistry*
  • Graphite / metabolism
  • Graphite / pharmacology*
  • Graphite / therapeutic use
  • Hepatitis / drug therapy*
  • Hepatitis / immunology*
  • Hepatitis / metabolism
  • Hepatitis / pathology
  • Humans
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Particle Size*
  • Quantum Dots / chemistry*


  • Biomarkers
  • Concanavalin A
  • Graphite