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

Aljabali, Alaa A. A.; 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.; Davis, Benjamin G.

Authors

Alaa A. A. Aljabali

Francisco Perez-Balderas

Sander I. Van Kasteren

Alaa A.A. Aljabali

Kim Wals

SEBASTIEN SERRES Sebastien.Serres@nottingham.ac.uk
Assistant Professor in Metabolic Biochemistry

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

Benjamin G. Davis



Abstract

© The Author(s) 2017. 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.

Citation

Aljabali, A. A. A., Perez-Balderas, F., Van Kasteren, S. I., Aljabali, A. A., Wals, K., Serres, S., …Davis, B. G. (2017). Covalent assembly of nanoparticles as a peptidase-degradable platform for molecular MRI. Nature Communications, 8, 14254. https://doi.org/10.1038/ncomms14254

Journal Article Type Article
Acceptance Date Dec 8, 2016
Online Publication Date Feb 15, 2017
Publication Date Feb 15, 2017
Deposit Date Mar 8, 2017
Publicly Available Date Mar 29, 2024
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Article Number 14254
Pages 14254
DOI https://doi.org/10.1038/ncomms14254
Public URL http://www.ncbi.nlm.nih.gov/pubmed/28198362
Publisher URL https://www.nature.com/articles/ncomms14254

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