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

Gallo J, Kamaly N, Lavdas I, Stevens E, Nguyen QD, Wylezinska-Arridge M, Aboagye EO, Long NJ - Angew. Chem. Int. Ed. Engl. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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).

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In vitro and in vivo “clicking” NPs. Two complementary IONPs weredesigned to undergo a bioorthogonal reaction after cleavage by MMP enzymes, which exposes the azideor alkyne moieties on either set of NPs. MNP=magnetic nanoparticle, PEG=polyethyleneglycol.
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fig01: In vitro and in vivo “clicking” NPs. Two complementary IONPs weredesigned to undergo a bioorthogonal reaction after cleavage by MMP enzymes, which exposes the azideor alkyne moieties on either set of NPs. MNP=magnetic nanoparticle, PEG=polyethyleneglycol.

Mentions: The general concept is presented in Figure 1;these particles have a surface decorated with peptide ligands that target them to tumor sites. Theirstructure also contains peptide sequences cleavable by the MMP2/9 enzymes overexpressed intumors.3 The cleavage of the protease-specific peptidesexposes either azide or alkyne moieties on the NP surfaces, thereby allowing the particles toundergo a [3+2] cycloaddition reaction. This copper-free chemical reactionleads to self-assembly of the IONPs and the change in particle distribution has an effect on therelaxivity (r2) of the contrast agent. The relaxivity is higher afterassembly,11 thus resulting in improved contrast inT2-weighted MR images. Furthermore, the IONPs are PEGylated, thusleading to improved in vivo bioavailability.[16] The targetingligand incorporated on the surface of the IONPs is a cyclopentapeptide with affinity for the CXCR4receptor.17


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

Gallo J, Kamaly N, Lavdas I, Stevens E, Nguyen QD, Wylezinska-Arridge M, Aboagye EO, Long NJ - Angew. Chem. Int. Ed. Engl. (2014)

In vitro and in vivo “clicking” NPs. Two complementary IONPs weredesigned to undergo a bioorthogonal reaction after cleavage by MMP enzymes, which exposes the azideor alkyne moieties on either set of NPs. MNP=magnetic nanoparticle, PEG=polyethyleneglycol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321346&req=5

fig01: In vitro and in vivo “clicking” NPs. Two complementary IONPs weredesigned to undergo a bioorthogonal reaction after cleavage by MMP enzymes, which exposes the azideor alkyne moieties on either set of NPs. MNP=magnetic nanoparticle, PEG=polyethyleneglycol.
Mentions: The general concept is presented in Figure 1;these particles have a surface decorated with peptide ligands that target them to tumor sites. Theirstructure also contains peptide sequences cleavable by the MMP2/9 enzymes overexpressed intumors.3 The cleavage of the protease-specific peptidesexposes either azide or alkyne moieties on the NP surfaces, thereby allowing the particles toundergo a [3+2] cycloaddition reaction. This copper-free chemical reactionleads to self-assembly of the IONPs and the change in particle distribution has an effect on therelaxivity (r2) of the contrast agent. The relaxivity is higher afterassembly,11 thus resulting in improved contrast inT2-weighted MR images. Furthermore, the IONPs are PEGylated, thusleading to improved in vivo bioavailability.[16] The targetingligand incorporated on the surface of the IONPs is a cyclopentapeptide with affinity for the CXCR4receptor.17

Bottom Line: 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.

View Article: PubMed Central - PubMed

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).

Show MeSH
Related in: MedlinePlus