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Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

Nature Nanotechnology volume 8, pages 772–781 (2013)Cite this article

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Abstract

In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.

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Figure 1: Protein coronas and their composition are established rapidly.
Figure 2: Correlation analysis reveals distinct kinetic protein-binding modalities during corona evolution.
Figure 3: Rapid corona formation kinetically impacts nanopathophysiology.
Figure 4: Bioinformatic classification of corona components.

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Acknowledgements

This work was supported by Grants DFG-SPP1313 and DFG-SFB490/Z3 and by BMBF-NanoKon/NanoMed/MRCyte, Zeiss-ChemBioMed, University Mainz Forschungszentrum Immunologie, Research Center for Immunology and Stiftung Rheinland-Pfalz (NANOSCH, NanoScreen). We thank R. Spohrer for preparation of the manuscript sample, S. Schneider for technical assistance and R. Zellner for discussions.

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  1. Stefan Tenzer and Dominic Docter: These authors contributed equally

Authors and Affiliations

  1. Institute for Immunology, University Medical Center of Mainz, Langenbeckstrasse 1, Mainz, 55101, Germany

    Stefan Tenzer, Jörg Kuharev & Hansjörg Schild

  2. Molecular and Cellular Oncology/Mainz Screening Center, University Medical Center of Mainz, Langenbeckstrasse 1, Mainz, 55101, Germany

    Dominic Docter, Verena Fetz & Roland H. Stauber

  3. Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz, 55128, Germany

    Anna Musyanovych & Katharina Landfester

  4. Institute for Molecular Biology, University Duisburg-Essen, Universitätsstrasse 5, Essen, 45117, Germany

    Rouven Hecht & Shirley K. Knauer

  5. Department of Pharmaceutical Technology, Friedrich-Schiller University Jena, Otto-Schott-Strasse 41, Jena, 07745, Germany

    Florian Schlenk & Dagmar Fischer

  6. Center for Thrombosis and Hemostasis, University Medical Center of Mainz, Langenbeckstrasse 1, Mainz, 55101, Germany

    Klytaimnistra Kiouptsi & Christoph Reinhardt

  7. Institute of Microtechnology Mainz GmbH, Carl-Zeiss-Strasse 18-20, Mainz, 55129, Germany

    Anna Musyanovych & Michael Maskos

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Contributions

R.H.S., S.T. and D.D. conceived and designed the study. S.T., D.D., J.K., V.F., R.H., F.S., K.K. and S.K.K. performed the experiments. A.M., F.S., D.F., K.L. and M.M. synthesized and characterized nanoparticles. S.T., J.K., D.F., C.R., K.L., H.S., M.M., S.K.K. and R.H.S. analysed data. R.H.S., S.K.K. and S.T. wrote the manuscript and Supplementary Information.

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Correspondence to Stefan Tenzer or Roland H. Stauber.

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The authors declare no competing financial interests.

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Tenzer, S., Docter, D., Kuharev, J. et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nature Nanotech 8, 772–781 (2013). https://doi.org/10.1038/nnano.2013.181

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