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CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging

Title: CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging
Authors: Gallo, J
Kamaly, N
Lavdas, I
Stevens, E
Nguyen, Q
Wylezinska-Arridge, M
Aboagye, EO
Long, NJ
Item Type: Journal Article
Abstract: MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in vitro and T2 signal enhancements of around 160 % were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these ‘smart’ self-assembling nanomaterials.
Issue Date: 1-Sep-2014
Date of Acceptance: 15-Jul-2014
URI: http://hdl.handle.net/10044/1/26353
DOI: 10.1002/anie.201405442
ISSN: 1521-3773
Publisher: WILEY-VCH Verlag
Start Page: 9550
End Page: 9554
Journal / Book Title: Angewandte Chemie International Edition
Volume: 53
Issue: 36
Copyright Statement: © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Cancer Research UK
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Cancer Research UK
National Institute for Health Research
Cancer Research UK
Scottish Power Foundation
Medical Research Council (MRC)
Cancer Research UK
Cancer Research UK
Cancer Research UK
Engineering & Physical Science Research Council (EPSRC)
Cancer Research UK
Medical Research Council (MRC)
National Institute for Health Research
Commission of the European Communities
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
GlaxoSmithKline Services Unlimited
Cancer Research UK
US Army (US)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 10337
RDC04 79560
RDB01 79560
12011
RDB03 79560
G0700915
12196
NIHR/CS/009/009
9335
4700192622
MR/N020782/1
16584
WSCC_P34611
12993
C2536/A10337
12991
MR/J007986/1
EME/13/122/01
115151
RDC04 79560
MC_PC15028
Mark Buswell
22353
W81XWH-09-1-0097
RDC04 79560
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
click chemistry
imaging agents
nanoparticles
self-assembly
tumor targeting
FREE CLICK CHEMISTRY
MRI CONTRAST AGENTS
MATRIX METALLOPROTEINASES
IN-VITRO
CANCER
CXCR4
EXPRESSION
NANOCARRIER
METASTASIS
RELAXIVITY
click chemistry
imaging agents
nanoparticles
self-assembly
tumor targeting
Alkynes
Animals
Azides
Contrast Media
Magnetic Resonance Imaging
Magnetite Nanoparticles
Matrix Metalloproteinases
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Experimental
Receptors, CXCR4
Animals
Mice, Inbred BALB C
Mice
Mice, Nude
Neoplasms, Experimental
Azides
Alkynes
Matrix Metalloproteinases
Receptors, CXCR4
Contrast Media
Magnetic Resonance Imaging
Magnetite Nanoparticles
click chemistry
imaging agents
nanoparticles
self-assembly
tumor targeting
Click chemistry
Imaging agents
Nanoparticles
Self-assembly
Tumor targeting
Organic Chemistry
03 Chemical Sciences
Publication Status: Published
Online Publication Date: 2014-07-15
Appears in Collections:Department of Surgery and Cancer
Chemistry
Catalysis and Advanced Materials
Faculty of Medicine
Faculty of Natural Sciences



This item is licensed under a Creative Commons License Creative Commons