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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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Sequential surface functionalization of synthesized IONPs. AUA=11-aminoundecanoic acid;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphonooxy-ethylester; COGA=cyclooct-1-yn-3-glycolic acid; 4-APB=4-azidophenacyl bromide; MMPpept=DNP-Pro-Leu-Gly-Met-Trp-Ser-Arg;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphate; CXCR4pept=cNal-Gly-d-Tyr-Orn[PEG-NH2]-Arg.
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fig02: Sequential surface functionalization of synthesized IONPs. AUA=11-aminoundecanoic acid;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphonooxy-ethylester; COGA=cyclooct-1-yn-3-glycolic acid; 4-APB=4-azidophenacyl bromide; MMPpept=DNP-Pro-Leu-Gly-Met-Trp-Ser-Arg;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphate; CXCR4pept=cNal-Gly-d-Tyr-Orn[PEG-NH2]-Arg.

Mentions: Magnetite (Fe3O4) was chosen as the core material for the development ofthe IONPs18 and a monodispersed population of oleic acidcapped IONPs was prepared according to a reported method.19The particles were fully characterized by using standard techniques (Figures S1, S2and Data S3 in the Supporting Information). In the next part of the synthetic strategy, aseries of sequential surface functionalizations were performed (Figure 2 and Data S4), and the reaction sequences could be monitored by FTIRspectroscopy (Figure S5 and S6) and 1H NMR spectroscopy(Figure S7).


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)

Sequential surface functionalization of synthesized IONPs. AUA=11-aminoundecanoic acid;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphonooxy-ethylester; COGA=cyclooct-1-yn-3-glycolic acid; 4-APB=4-azidophenacyl bromide; MMPpept=DNP-Pro-Leu-Gly-Met-Trp-Ser-Arg;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphate; CXCR4pept=cNal-Gly-d-Tyr-Orn[PEG-NH2]-Arg.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Sequential surface functionalization of synthesized IONPs. AUA=11-aminoundecanoic acid;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphonooxy-ethylester; COGA=cyclooct-1-yn-3-glycolic acid; 4-APB=4-azidophenacyl bromide; MMPpept=DNP-Pro-Leu-Gly-Met-Trp-Ser-Arg;P-PEG7-N3=O-(2-azidoethyl)heptaethylene glycol phosphate; CXCR4pept=cNal-Gly-d-Tyr-Orn[PEG-NH2]-Arg.
Mentions: Magnetite (Fe3O4) was chosen as the core material for the development ofthe IONPs18 and a monodispersed population of oleic acidcapped IONPs was prepared according to a reported method.19The particles were fully characterized by using standard techniques (Figures S1, S2and Data S3 in the Supporting Information). In the next part of the synthetic strategy, aseries of sequential surface functionalizations were performed (Figure 2 and Data S4), and the reaction sequences could be monitored by FTIRspectroscopy (Figure S5 and S6) and 1H NMR spectroscopy(Figure S7).

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