Abstract
Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties1 may change upon internalization by cells2,3. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles (198Au)4 and engineered an 111In-labelled polymer shell around them5. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for 198Au and 111In showed partial removal of the polymer shell in vivo. While 198Au accumulates mostly in the liver, part of the 111In shows a non-particulate biodistribution similar to intravenous injection of chelated 111In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.
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Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (DFG grant ‘PA794/11-1’ to W.J.P., grant ‘SPP1313’ to W.G.K.) and the European Commission Seventh Framework Programme (EC-FP7 grant ‘ENPRA NMP4-SL-2009-228789’ and ‘Neuronano NMP4-SL-2008-214547’ to W.G.K.). The authors would like to thank N. Senger, S. Kaidel, B. Kupferschmid and B. Krieger for technical assistance and to D. Hühn, R. Gill, M. Klapper and K. Dawson for scientific discussions.
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W.G.K. and W.J.P. conceived the idea, designed and analysed the experiments, and mainly wrote the manuscript. All authors discussed the results, contributed to data analysis, and commented on the manuscript. A.M.A., Z.A., J.M.M., T.R. and I.R.d.L. prepared and characterized the nanoparticles. R.H., K.K., D.J.d.A. and J.R. performed the in vitro experiments. A.W., N.H., S.H. and G.K.S. carried out in vivo experiments with radionucleotides. F.A. and R.U. carried out in vivo experiments with fluorescent nanoparticles. M.G. performed transmission electron microscopy measurements.
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Kreyling, W., Abdelmonem, A., Ali, Z. et al. In vivo integrity of polymer-coated gold nanoparticles. Nature Nanotech 10, 619–623 (2015). https://doi.org/10.1038/nnano.2015.111
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DOI: https://doi.org/10.1038/nnano.2015.111
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