title: CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging.
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.
authors.affiliation: Comprehensive Cancer Imaging Centre, Department of Surgery and Cancer, Hammersmith Campus, Imperial College London, Du Cane Road, London, W12 0NN (UK); Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ (UK).
authors.forename: Juan
authors.initials: J
authors.lastname: Gallo
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.forename: Ioannis
authors.initials: I
authors.lastname: Lavdas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stevens
authors.forename: Quang-De
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Marzena
authors.initials: M
authors.lastname: Wylezinska-Arridge
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Long
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D020782:Matrix Metalloproteinases / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology; D019718:Receptors, CXCR4 / Q000187:drug effects*
chemical_list: D000480:Alkynes; D001386:Azides; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D019718:Receptors, CXCR4; D020782:Matrix Metalloproteinases
keywords: click chemistry; imaging agents; nanoparticles; self-assembly; tumor targeting