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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.
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
9c482337-f054-4c82-9034-216a86d5e0ab
van Kasteren, Sander I.
3faf410a-23ee-4eb2-ab44-4fbd0a7e0c90
Aljabali, Alaa A. A.
dcb22453-4feb-43ea-a2a4-61a972184753
Wals, Kim
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Serres, Sebastien
83515636-b849-493f-8961-9b537d6003af
Jefferson, Andrew
200c62ac-0659-4ee5-b589-bb849a33e966
Sarmiento Soto, Manuel
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Khrapitchev, Alexandre A.
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Larkin, James R.
021c7d55-27a6-48a7-bad0-03e09b3417b2
Bristow, Claire
ce03b98a-7e1a-4dec-be9d-7f2bedab3532
Lee, Seung Seo
ee34fa26-5fb6-48c8-80c2-1f13ec4ccceb
Bort, Guillaume
f7e96e44-5054-4595-9510-10e193f9c123
De Simone, Filippo
414c10fd-ea23-4206-bcb8-1df64aee5669
Campbell, Sandra J.
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Choudhury, Robin P.
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Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Sibson, Nicola R.
408b5626-2da8-4fc8-9fb5-bbe52a7b8aaf
Davis, Benjamin G.
2a8a594f-5d71-455a-bd99-d1366c1028cc

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).

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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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: http://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: 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: 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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