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In vivo integrity of polymer-coated gold nanoparticles

Nature Nanotechnology volume 10, pages 619–623 (2015)Cite this article

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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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Figure 1: Sketch of double-radiolabelled nanoparticles.
Figure 2: Biodistribution of double-labelled nanoparticles.
Figure 3: Quantitative biodistribution of soluble free 111In ions and 111In–DPTA complexes.
Figure 4: Cellular internalization and degradation of polymer-coated Au nanoparticles and QDs by proteases ‘in test tube’ and in vitro.
Figure 5: Quantitative 24 h biodistribution of intravenously injected coated Au nanoparticles.

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References

  1. Rivera Gil, P. et al. The challenge to relate the physicochemical properties of colloidal nanoparticles to their cytotoxicity. Acc. Chem. Res. 46, 743–749 (2013).

    Article  CAS  Google Scholar 

  2. Chanana, M., Rivera Gil, P., Correa-Duarte, M. A., Parak, W. J. & Liz-Marzán, L. M. Physicochemical properties of protein-coated gold nanoparticles in biological fluids and cells before and after proteolytic digestion. Angew. Chem. Int. Ed. 52, 4179–4183 (2013).

    Article  CAS  Google Scholar 

  3. Chen, H. W., Zou, P., Connarn, J., Paholak, H. & Sun, D. X. Intracellular dissociation of a polymer coating from nanoparticles. Nano Res. 5, 815–825 (2012).

    Article  CAS  Google Scholar 

  4. Semmler-Behnke, M. et al. Biodistribution of 1.4- and 18-nm gold particles in rats. Small 4, 2108–2111 (2008).

    Article  CAS  Google Scholar 

  5. Ali, Z. et al. Multifunctional nanoparticles for dual imaging. Anal. Chem. 83, 2877–2882 (2011).

    Article  CAS  Google Scholar 

  6. Kreyling, W. G. et al. Interspecies comparison of phagolysosomal pH in alveolar acrophages. Inhal. Toxicol. 3, 91–100 (1991).

    Article  Google Scholar 

  7. Soenen, S. J. H. et al. Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality. Small 6, 2136–2145 (2010).

    Article  CAS  Google Scholar 

  8. Levy, M. et al. Long term in vivo biotransformation of iron oxide nanoparticles. Biomaterials 32, 3988–3999 (2011).

    Article  CAS  Google Scholar 

  9. Derfus, A. M., Chan, W. C. W. & Bhatia, S. N. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11–18 (2004).

    Article  CAS  Google Scholar 

  10. Kirchner, C. et al. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 5, 331–338 (2005).

    Article  CAS  Google Scholar 

  11. Kittler, S., Greulich, C., Diendorf, J., Koller, M. & Epple, M. Toxicity of silver nanoparticles increases during storage because of slow dissolution under release of silver ions. Chem. Mater. 22, 4548–4554 (2010).

    Article  CAS  Google Scholar 

  12. Caballero-Díaz, E. et al. The toxicity of silver nanoparticles depends on their uptake by cells and thus on their surface chemistry. Part. Part. Syst. Charact. 30, 1079–1085 (2013).

    Article  Google Scholar 

  13. Bose, K., Koch, M., Cavelius, C., Kiemer, A. K. & Kraegeloh, A. A correlative analysis of gold nanoparticles internalized by A549 cells. Part. Part. Syst. Charact. 31, 439–448 (2014).

    Article  Google Scholar 

  14. Lunov, O. et al. Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. Biomaterials 31, 9015–9022 (2010).

    Article  CAS  Google Scholar 

  15. Tietze, R. et al. Efficient drug-delivery using magnetic nanoparticles—biodistribution and therapeutic effects in tumour bearing rabbits. Nanomed. Nanotechnol. 9, 961–971 (2013).

    Article  CAS  Google Scholar 

  16. Ducongé, F. et al. Fluorine-18-labeled phospholipid quantum dot micelles for in vivo multimodal imaging from whole body to cellular scales. Bioconj. Chem. 19, 1921–1926 (2008).

    Article  Google Scholar 

  17. Sée, V. et al. Cathepsin l digestion of nanobioconjugates upon endocytosis. ACS Nano 3, 2461–2468 (2009).

    Article  Google Scholar 

  18. Wang, F. et al. The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes. Nanomed. Nanotechnol. 9, 1159–1168 (2013).

    Article  CAS  Google Scholar 

  19. Schleh, C. et al. Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration. Nanotoxicology 6, 36–46 (2012).

    Article  CAS  Google Scholar 

  20. Hirn, S. et al. Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. Eur. J. Pharm. Biopharm. 77, 407–416 (2011).

    Article  CAS  Google Scholar 

  21. Oeff, K., Krentz, K. & Kessel, M. J-131-Clearance der normalen und pathologischen Magenschleimhaut. Klin. Wochenschr. 33, 59–63 (1955).

    Article  CAS  Google Scholar 

  22. Kreyling, W. G. et al. Air–blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size. ACS Nano 8, 222–233 (2014).

    Article  CAS  Google Scholar 

  23. Lipka, M. et al. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials 31, 6574–6581 (2010).

    Article  CAS  Google Scholar 

  24. Pan, Y. et al. Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small 5, 2067–2076 (2009).

    Article  CAS  Google Scholar 

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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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Author notes

  1. Zulqurnain Ali, Nadine Haberl, Stephanie Hirn, Gülnaz Khadem-Saba & Jose-Maria Montenegro

    Present address: Present addresses: Department of Physics, Air University, Sector E-9, Islamabad 44000, Pakistan (Z.A.); Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich 81377, Germany (S.H., N.H.); Department of Chemistry, Industrial Biocatalysis, Technische Universität München (TUM), Garching 85748, Germany (G.K-S.); Andalusian Centre for Nanomedicine & Biotechnology-BIONAND and Universidad de Malaga-IBIMA, Malaga 29071, Spain (J-M.M.),

Authors and Affiliations

  1. Institute of Lung Biology and Disease and Institute of Epidemiology 2, Helmholtz Zentrum München – German Research for Center for Environmental Health, Neuherberg/Munich, 85764, Germany

    Wolfgang G. Kreyling, Nadine Haberl, Stephanie Hirn, Gülnaz Khadem-Saba & Alexander Wenk

  2. Department of Physics, Philipps Universität Marburg, Marburg, 35032, Germany

    Abuelmagd M. Abdelmonem, Zulqurnain Ali, Raimo Hartmann, Dorleta Jimenez de Aberasturi, Karsten Kantner, Jose-Maria Montenegro, Joanna Rejman & Wolfgang J. Parak

  3. Department of Molecular Biology of Neuronal Signals, Max Planck Institute of Experimental Medicine, Göttingen, 37075, Germany

    Frauke Alves & Roser Ufartes

  4. Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, 37075, Germany

    Frauke Alves

  5. Institute of Anatomy, University of Bern, Bern, 3012, Switzerland

    Marianne Geiser

  6. Department of Inorganic Chemistry, UPV/EHU, Bilbao 48080, Spain, Department of Inorganic Chemistry, UPV/EHU, Bilbao 48080, Spain; CIC-Energigune, Miñano 01510,

    Dorleta Jimenez de Aberasturi, Teofilo Rojo & Idoia Ruiz de Larramendi

  7. CIC-Energigune, Miñano 01510, Spain

    Dorleta Jimenez de Aberasturi, Teofilo Rojo & Idoia Ruiz de Larramendi

  8. CIC Biomagune, San Sebastian, 20009, Spain

    Dorleta Jimenez de Aberasturi & Wolfgang J. Parak

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  1. Wolfgang G. Kreyling
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Contributions

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.

Corresponding authors

Correspondence to Wolfgang G. Kreyling or Wolfgang J. Parak.

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The authors declare no competing financial interests.

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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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