1. CXCR4-Targeted and MMP-Responsive Iron Oxide Nanoparticles for Enhanced Magnetic Resonance Imaging
- Author
-
Gallo, J, Kamaly, N, Lavdas, I, Stevens, E, Nguyen, Q, Wylezinska-Arridge, M, Aboagye, EO, Long, NJ, Cancer Research UK, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), National Institute for Health Research, Scottish Power Foundation, Engineering & Physical Science Research Council (EPSRC), Commission of the European Communities, GlaxoSmithKline Services Unlimited, and US Army (US)
- Subjects
EXPRESSION ,Azides ,Receptors, CXCR4 ,RELAXIVITY ,Chemistry, Multidisciplinary ,Contrast Media ,Mice, Nude ,NANOCARRIER ,Tumor Imaging ,FREE CLICK CHEMISTRY ,Mice ,Animals ,Magnetite Nanoparticles ,CXCR4 ,Mice, Inbred BALB C ,Science & Technology ,tumor targeting ,Communication ,Organic Chemistry ,MRI CONTRAST AGENTS ,IN-VITRO ,self-assembly ,Neoplasms, Experimental ,General Medicine ,CANCER ,Magnetic Resonance Imaging ,Matrix Metalloproteinases ,imaging agents ,Chemistry ,Alkynes ,Physical Sciences ,METASTASIS ,click chemistry ,nanoparticles ,03 Chemical Sciences - 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.
- Published
- 2014
- Full Text
- View/download PDF