Alaa A. A. Aljabali
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
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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Covalent assembly of nanoparticles
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