Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI
Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI
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.
Perez-Balderas, Francisco
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van Kasteren, Sander I.
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Aljabali, Alaa A. A.
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Wals, Kim
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Serres, Sebastien
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Jefferson, Andrew
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Sarmiento Soto, Manuel
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Khrapitchev, Alexandre A.
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Larkin, James R.
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Bristow, Claire
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Lee, Seung Seo
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Bort, Guillaume
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De Simone, Filippo
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Campbell, Sandra J.
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Choudhury, Robin P.
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Anthony, Daniel C.
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Sibson, Nicola R.
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Davis, Benjamin G.
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15 February 2017
Perez-Balderas, Francisco
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van Kasteren, Sander I.
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Aljabali, Alaa A. A.
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Wals, Kim
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Serres, Sebastien
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Jefferson, Andrew
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Sarmiento Soto, Manuel
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Khrapitchev, Alexandre A.
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Larkin, James R.
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Bristow, Claire
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Lee, Seung Seo
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Bort, Guillaume
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De Simone, Filippo
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Campbell, Sandra J.
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Choudhury, Robin P.
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Anthony, Daniel C.
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Sibson, Nicola R.
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Davis, Benjamin G.
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Perez-Balderas, Francisco, van Kasteren, Sander I., Aljabali, Alaa A. A., Wals, Kim, Serres, Sebastien, Jefferson, Andrew, Sarmiento Soto, Manuel, Khrapitchev, Alexandre A., Larkin, James R., Bristow, Claire, Lee, Seung Seo, Bort, Guillaume, De Simone, Filippo, Campbell, Sandra J., Choudhury, Robin P., Anthony, Daniel C., Sibson, Nicola R. and Davis, Benjamin G.
(2017)
Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI.
Nature Communications, 8, [14254].
(doi:10.1038/ncomms14254).
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.
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Accepted/In Press date: 8 December 2016
e-pub ahead of print date: 15 February 2017
Published date: 15 February 2017
Organisations:
Chemical Biology Group
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Local EPrints ID: 405742
URI: http://eprints.soton.ac.uk/id/eprint/405742
PURE UUID: 90dab4e7-1bb3-4467-9123-b101738d991a
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Date deposited: 18 Feb 2017 00:21
Last modified: 16 Mar 2024 05:01
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Contributors
Author:
Francisco Perez-Balderas
Author:
Sander I. van Kasteren
Author:
Alaa A. A. Aljabali
Author:
Kim Wals
Author:
Sebastien Serres
Author:
Andrew Jefferson
Author:
Manuel Sarmiento Soto
Author:
Alexandre A. Khrapitchev
Author:
James R. Larkin
Author:
Claire Bristow
Author:
Guillaume Bort
Author:
Filippo De Simone
Author:
Sandra J. Campbell
Author:
Robin P. Choudhury
Author:
Daniel C. Anthony
Author:
Nicola R. Sibson
Author:
Benjamin G. Davis
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