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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.


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

Show Author's information Rafael G. Mendes1,2Angelo Mandarino2Britta Koch2Anne K. Meyer2Alicja Bachmatiuk1,2,3Cordula Hirsch4Thomas Gemming2Oliver G. Schmidt2,5Zhongfan Liu1,6Mark H. Rümmeli1,2,3( )
College of PhysicsOptoelectronics and Energy & Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow UniversitySuzhou215006China
IFW DresdenInstitute for Solid State and Materials ResearchP.O. Box D-01171, DresdenGermany
Centre of Polymer and Carbon MaterialsPolish Academy of Sciences, M. Curie-Sklodowskiej 34, Zabrze, 41-819Poland
EMPA - Swiss Federal Laboratories for Materials Science and TechnologyLerchenfeldstrasse 59014St. Gallen, Switzerland
Material Systems for NanoelectronicsChemnitz University of TechnologyReichenhainer Str. 7009107Chemnitz, Germany
Center for NanochemistryBeijing Science and Engineering Centre for NanocarbonsBeijing National Laboratory for Molecular SciencesCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871China

Abstract

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.

Keywords: graphene oxide, uptake, label-free, THP-1 cells, size dependence

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Publication history
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Acknowledgements

Publication history

Received: 29 September 2016
Revised: 18 November 2016
Accepted: 21 November 2016
Published: 05 January 2017
Issue date: June 2017

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

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.

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