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Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging

Nature Materials volume 9, pages 485–490 (2010)Cite this article

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Abstract

Functionalization of nanomaterials for precise biomedical function is an emerging trend in nanotechnology1. Carbon nanotubes are attractive as multifunctional carrier systems because payload can be encapsulated in internal space whilst outer surfaces can be chemically modified2. Yet, despite potential as drug delivery systems3,4 and radiotracers5,6,7,8, such filled-and-functionalized carbon nanotubes have not been previously investigated in vivo. Here we report covalent functionalization of radionuclide-filled single-walled carbon nanotubes and their use as radioprobes. Metal halides, including Na125I, were sealed inside single-walled carbon nanotubes to create high-density radioemitting crystals9 and then surfaces of these filled–sealed nanotubes were covalently modified with biantennary carbohydrates, improving dispersibility and biocompatibility10. Intravenous administration of Na125I-filled glyco-single-walled carbon nanotubes in mice was tracked in vivo using single-photon emission computed tomography. Specific tissue accumulation (here lung) coupled with high in vivo stability prevented leakage of radionuclide to high-affinity organs (thyroid/stomach) or excretion, and resulted in ultrasensitive imaging and delivery of unprecedented radiodose density. Nanoencapsulation of iodide within single-walled carbon nanotubes enabled its biodistribution to be completely redirected from tissue with innate affinity (thyroid) to lung. Surface functionalization of 125I-filled single-walled carbon nanotubes offers versatility towards modulation of biodistribution of these radioemitting crystals in a manner determined by the capsule that delivers them. We envisage that organ-specific therapeutics and diagnostics can be developed on the basis of the nanocapsule model described here.

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Figure 1: Preparation of the construct.
Figure 2: Simultaneous detection of filling and functionalization.
Figure 3: Whole-animal SPECT/CT imaging, tissue biodistribution, blood circulation and histology following intravenous administration of filled, functionalized SWNTs.

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Acknowledgements

We thank the Samsung Scholarship Foundation (S.Y.H.), the FP7 European Community Marie Curie ERG and Ramón y Cajal Programmes (G.T.), MICINN Spain (B.B.), INSS Japan (S.L-P.) and Thomas Swan Co. Ltd. (SWNTs and funding), and K. Doores, O. Pearce, J. Errey, W. Liu and M. A. Ward for technical assistance. R.B.S. is a member of the European Community CARBIO research training network. K.K. and K.T.A-J. would like to acknowledge partial funding of this work by the FP7 Anticarb (HEALTH-2007-201587) research programme. H.A-B. wishes to acknowledge the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique (Algeria) for a full Ph.D. scholarship. B.G.D. is a Royal Society–Wolfson Research Merit Award recipient and is supported by an EPSRC LSI platform grant.

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Authors and Affiliations

  1. Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK

    Sung You Hong & Benjamin G. Davis

  2. Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford OX1 3QR, UK

    Gerard Tobias, Belén Ballesteros & Malcolm L. H. Green

  3. Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Barcelona, Spain

    Gerard Tobias

  4. Nanomedicine Lab, Centre for Drug Delivery Research, The School of Pharmacy, University of London, London WC1N 1AX, UK

    Khuloud T. Al-Jamal, Hanene Ali-Boucetta & Kostas Kostarelos

  5. Centre d’Investigació en Nanociència i Nanotecnologia (ICN-CSIC), Campus UAB, 08193 Bellaterra, Barcelona, Spain

    Belén Ballesteros

  6. Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH, UK

    Sergio Lozano-Perez & Peter D. Nellist

  7. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK

    Robert B. Sim

  8. Department of Nuclear Medicine, St Bartholomew’s Hospital, London EC1A 7BE, UK

    Ciara Finucane & Stephen J. Mather

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  1. Sung You Hong
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Contributions

S.Y.H., G.T., R.B.S., M.L.H.G., K.K. and B.G.D. designed the research, S.Y.H., G.T., K.T.A-J., B.B., H.A-B., S.L-P., C.F. and S.J.M. carried out the experiments, S.Y.H., G.T., K.T.A-J., H.A-B., B.B., S.L-P., P.D.N., R.B.S., S.J.M., M.L.H.G., K.K. and B.G.D. analysed the data and S.Y.H., G.T., K.T.A-J., K.K. and B.G.D. wrote the paper.

Corresponding authors

Correspondence to Gerard Tobias, Kostas Kostarelos or Benjamin G. Davis.

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Hong, S., Tobias, G., Al-Jamal, K. et al. Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging. Nature Mater 9, 485–490 (2010). https://doi.org/10.1038/nmat2766

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