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

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 Bristow, Seung Seo Lee, Guillaume Bort, Filippo De Simone, Sandra J. Campbell, Robin P. Choudhury, Daniel C. Anthony (), Nicola R. Sibson () and Benjamin G. Davis ()
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Francisco Perez-Balderas: Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
Sander I. van Kasteren: Chemistry Research Laboratory, University of Oxford
Alaa A. A. Aljabali: Chemistry Research Laboratory, University of Oxford
Kim Wals: Chemistry Research Laboratory, University of Oxford
Sébastien Serres: Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
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
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

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14254

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