Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 36, Pages 9550-9554Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201405442
Keywords
click chemistry; imaging agents; nanoparticles; self-assembly; tumor targeting
Categories
Funding
- CRUK
- EPSRC
- MRC
- Department of Health [C2536/A10337]
- MRC [MR/J007986/1, MC_U120081322] Funding Source: UKRI
- Cancer Research UK [12011, 16584, 10337] Funding Source: researchfish
- Medical Research Council [MC_U120081322, MR/J007986/1] Funding Source: researchfish
- National Institute for Health Research [NIHR/CS/009/009] Funding Source: researchfish
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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 T-2 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 T-2 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.
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