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Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI

Author

Listed:
  • Francisco Perez-Balderas

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
    Chemistry Research Laboratory, University of Oxford)

  • Sander I. van Kasteren

    (Chemistry Research Laboratory, University of Oxford
    Present address: Gorlaeus Laboratory, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, The Netherlands)

  • Alaa A. A. Aljabali

    (Chemistry Research Laboratory, University of Oxford
    University of Oxford, John Radcliffe Hospital
    Present address: Pharmacy Department, Yarmouk University, Irbid, Jordan)

  • Kim Wals

    (Chemistry Research Laboratory, University of Oxford
    University of Oxford)

  • Sébastien Serres

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
    Present address: School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK)

  • Andrew Jefferson

    (University of Oxford, John Radcliffe Hospital)

  • Manuel Sarmiento Soto

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • Alexandre A. Khrapitchev

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • James R Larkin

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • Claire Bristow

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • Seung Seo Lee

    (Chemistry Research Laboratory, University of Oxford
    Present address: School of Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK)

  • Guillaume Bort

    (Chemistry Research Laboratory, University of Oxford)

  • Filippo De Simone

    (Chemistry Research Laboratory, University of Oxford)

  • Sandra J. Campbell

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • Robin P. Choudhury

    (University of Oxford, John Radcliffe Hospital)

  • Daniel C. Anthony

    (University of Oxford)

  • Nicola R. Sibson

    (Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford)

  • Benjamin G. Davis

    (Chemistry Research Laboratory, University of Oxford)

Abstract

Ligand-conjugated microparticles of iron oxide (MPIO) have the potential to provide high sensitivity contrast for molecular magnetic resonance imaging (MRI). However, the accumulation and persistence of non-biodegradable micron-sized particles in liver and spleen precludes their clinical use and limits the translational potential of MPIO-based contrast agents. Here we show that ligand-targeted MPIO derived from multiple iron oxide nanoparticles may be coupled covalently through peptide linkers that are designed to be cleaved by intracellular macrophage proteases. The synthesized particles possess potential characteristics for targeted MRI contrast agents, including high relaxivity, unappreciable sedimentation, clearance from circulation and no overt toxicity. Importantly, we demonstrate that these particles are rapidly degraded both in vitro and in vivo, and that the targeted probes can be used for detection of inflammation in vivo using MRI. This approach provides a platform for molecular MRI contrast agents that is potentially more suitable for translation to humans.

Suggested Citation

  • Francisco Perez-Balderas & Sander I. van Kasteren & Alaa A. A. Aljabali & Kim Wals & Sébastien Serres & Andrew Jefferson & Manuel Sarmiento Soto & Alexandre A. Khrapitchev & James R Larkin & Claire Br, 2017. "Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14254
    DOI: 10.1038/ncomms14254
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    Cited by:

    1. Charlène Jacqmarcq & Audrey Picot & Jules Flon & Florent Lebrun & Sara Martinez de Lizarrondo & Mikaël Naveau & Benoît Bernay & Didier Goux & Marina Rubio & Aurélie Malzert-Fréon & Anita Michel & Fabi, 2024. "MRI-based microthrombi detection in stroke with polydopamine iron oxide," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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