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Issue 68, 2016
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Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time magnetic resonance imaging

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Abstract

We report on the synthesis, characterization, stability and pharmacokinetics of novel iron based contrast agents for magnetic resonance imaging (MRI). Statistical copolymers combining multiple phosphonic acid groups and poly(ethylene glycol) (PEG) were synthesized and used as coating agents for 10 nm iron oxide nanocrystals. In vitro, protein corona and stability assays show that phosphonic acid PEG copolymers outperform all other coating types examined, including low molecular weight anionic ligands and polymers. In vivo, the particle pharmacokinetics is investigated by monitoring the MRI signal intensity from mouse liver, spleen and arteries as a function of time, between one minute and seven days after injection. Iron oxide particles coated with multi-phosphonic acid PEG polymers are shown to have a blood circulation lifetime of 250 minutes, i.e. 10 to 50 times greater than that of recently published PEGylated probes and benchmarks. The clearance from the liver takes in average 2 to 3 days and is independent of the core size, coating and particle stability. By comparing identical core particles with different coatings, we are able to determine the optimum conditions for stealth MRI probes.

Graphical abstract: Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time magnetic resonance imaging

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Supplementary files

Article information


Submitted
16 Apr 2016
Accepted
24 Jun 2016
First published
29 Jun 2016

RSC Adv., 2016,6, 63788-63800
Article type
Paper

Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time magnetic resonance imaging

G. Ramniceanu, B.-T. Doan, C. Vezignol, A. Graillot, C. Loubat, N. Mignet and J.-F. Berret, RSC Adv., 2016, 6, 63788
DOI: 10.1039/C6RA09896G

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