Nanoparticle-mediated cellular response is size-dependent

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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.

Author information

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.

Correspondence to Warren C. W. Chan.

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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) doi:10.1038/nnano.2008.30

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