Nano Research

, Volume 10, Issue 6, pp 1980–1995 | Cite as

Size and time dependent internalization of label-free nano-graphene oxide in human macrophages

  • Rafael G. Mendes
  • Angelo Mandarino
  • Britta Koch
  • Anne K. Meyer
  • Alicja Bachmatiuk
  • Cordula Hirsch
  • Thomas Gemming
  • Oliver G. Schmidt
  • Zhongfan Liu
  • Mark H. RümmeliEmail author
Research Article


Graphene oxide shows great promise as a material for biomedical applications, e.g., as a multi-drug delivery platform. With this in view, reports of studies on the interaction between nanosized graphene oxide flakes and biological cells are beginning to emerge. However, the number of studies remains limited, and most used labeled graphene oxide samples to track the material upon endocytosis. Unfortunately, the labeling process alters the surface functionality of the graphene oxide, and this additional functionalization has been shown to alter the cellular response. Hence, in this work we used label-free graphene oxide. We carefully tracked the uptake of three different nanoscale graphene oxide flake size distributions using scanning/transmission electron microscopy. Uptake was investigated in undifferentiated human monocyte cells (THP-1) and differentiated macrophage cells. The data show clear size dependence for uptake, such that larger graphene oxide flakes (and clusters) are more easily taken up by the cells compared to smaller flakes. Moreover, uptake is shown to occur very rapidly, within two min of incubation with THP-1 cells. The data highlights a crucial need for cellular incubation studies with nanoparticles, to be conducted for short incubation periods as certain dependencies (e.g., size and concentration) are lost with longer incubation periods.


graphene oxide THP-1 cells label-free uptake size dependence 


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A. B. and M. H. R. thank the EOARD for support. A. B. thanks the National Science Centre for the financial support within the frames of the Sonata Program (Grant agreement 2014/13/D/ST5/02853). M. H. R. thanks the National Natural Science Foundation of China (No. 51672181). M. H. R., R. G. M. and A. M. conceived the experiments, prepared samples and collected the data. All authors were involved in the design of the experiments, analysis of the data and manuscript preparation.

Supplementary material

12274_2016_1385_MOESM1_ESM.pdf (5.4 mb)
Size and time dependent internalization of label-free nano-graphene oxide in human macrophages


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Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Rafael G. Mendes
    • 1
    • 2
  • Angelo Mandarino
    • 2
  • Britta Koch
    • 2
  • Anne K. Meyer
    • 2
  • Alicja Bachmatiuk
    • 1
    • 2
    • 3
  • Cordula Hirsch
    • 4
  • Thomas Gemming
    • 2
  • Oliver G. Schmidt
    • 2
    • 5
  • Zhongfan Liu
    • 1
    • 6
  • Mark H. Rümmeli
    • 1
    • 2
    • 3
    Email author
  1. 1.College of Physics, Optoelectronics and Energy & Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow UniversitySuzhouChina
  2. 2.IFW Dresden, Institute for Solid State and Materials ResearchDresdenGermany
  3. 3.Centre of Polymer and Carbon MaterialsPolish Academy of SciencesZabrzePoland
  4. 4.EMPA - Swiss Federal Laboratories for Materials Science and TechnologySt. GallenSwitzerland
  5. 5.Material Systems for NanoelectronicsChemnitz University of TechnologyChemnitzGermany
  6. 6.Center for Nanochemistry, Beijing Science and Engineering Centre for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina

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