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

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.
1-10
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
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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.
408b5626-2da8-4fc8-9fb5-bbe52a7b8aaf
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, 1-10. (doi:10.1038/ncomms14254).

Record type: Article

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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More information

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

Identifiers

Local EPrints ID: 405742
URI: https://eprints.soton.ac.uk/id/eprint/405742
PURE UUID: 90dab4e7-1bb3-4467-9123-b101738d991a
ORCID for Seung Seo Lee: ORCID iD orcid.org/0000-0002-8598-3303

Catalogue record

Date deposited: 18 Feb 2017 00:21
Last modified: 20 Mar 2019 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: Seung Seo Lee ORCID iD
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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