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Nanoparticle-mediated cellular response is size-dependent

Nature Nanotechnology volume 3, pages 145–150 (2008)Cite this article

Abstract

Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics1,2,3,4,5,6. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2–100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death)7, 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.

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Figure 1: Specific interactions between Her–GNPs and ErbB2 receptors determine their internalization fate.
Figure 2: Dependence of ErbB2 receptor internalization on nanoparticle size.
Figure 3: Dependence of downregulation of membrane ErbB2 expression on nanoparticle size.
Figure 4: Influence of different-sized nanoparticles on downstream protein expression.

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Acknowledgements

Financial support was provided by the Canadian Institutes of Health Research (W.C.W.C. and J.T.R.), Natural Sciences and Engineering Council of Canada (W.J., B.Y.S.K. and W.C.W.C.), Canadian Foundation for Innovation and Ontario Innovation Trust (W.C.W.C.), the Surgeon Scientist Program and the Ontario Ministry of Health (B.Y.S.K.). The authors wish to thank J. Klonstranec for helpful discussions, A. Manseur and T. Jennings for help with flow cytometry, B. Calvieri, S. Doyle and D. Holmyard with cell preparation for electron microscopy, and J. Oreopoulos from the Yip lab with confocal microscopy.

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Authors and Affiliations

  1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, M5S 3G9, Ontario, Canada

    Wen Jiang, Betty Y. S. Kim & Warren C. W. Chan

  2. Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, M5S 3E1, Ontario, Canada

    Wen Jiang, Betty Y. S. Kim & Warren C. W. Chan

  3. Division of Neurosurgery, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada

    Betty Y. S. Kim & James T. Rutka

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  1. Wen Jiang
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Contributions

W.J., B.Y.S.K. and W.C.W.C designed the experiments. W.J. and B.Y.S.K. performed the experiments and gathered the data. All authors discussed the results, co-wrote the paper and commented on the manuscript. W.J. and B.Y.S.K. contributed equally to this work.

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Jiang, W., Kim, B., Rutka, J. et al. Nanoparticle-mediated cellular response is size-dependent. Nature Nanotech 3, 145–150 (2008). https://doi.org/10.1038/nnano.2008.30

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