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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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A) Results from the analyses of T2 maps from a series of spinecho images acquired with different TEs. Only the region of interest comprising thetumor was considered for the analyses. B) Iron concentrations in the different organsmeasured 48 h after the injection of targeted NPs. The results are expressed as the mean ofthree independent experiments ±the standard deviation. *=statisticallydifferent with p<0.05, S. Int=small intestine,L. Int=large intestine. Representative tumor T2 maps areshown from a series of spin echo images acquired with different TEs before (C) and4 h after (D) the intravenous injection of targeted NPs. Color bar scale in milliseconds.
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fig05: A) Results from the analyses of T2 maps from a series of spinecho images acquired with different TEs. Only the region of interest comprising thetumor was considered for the analyses. B) Iron concentrations in the different organsmeasured 48 h after the injection of targeted NPs. The results are expressed as the mean ofthree independent experiments ±the standard deviation. *=statisticallydifferent with p<0.05, S. Int=small intestine,L. Int=large intestine. Representative tumor T2 maps areshown from a series of spin echo images acquired with different TEs before (C) and4 h after (D) the intravenous injection of targeted NPs. Color bar scale in milliseconds.

Mentions: Next, mice bearing tumors were intravenously injected with a mixture of the two populations ofNPs in the same needle. Results from mice (n=3) injected with targeted IONPsrevealed that the T2 relaxation time of the entire tumor had decreasedby approximately 14 % at 4 h after injection (Figure 5 A,C,D). Control nontargeted NPs and saline injections didnot produce any significant change in tumor contrast after 4 h(ΔT2∼0.4 %). Signal measurements from thebody T2-w images showed a decrease in the ratio of liver-to-brain signalboth with targeted and control nontargeted NPs, thus confirming the accumulation of NPs in the liverarea (Figure S10 C,D). To corroborate the MRI findings, the animals were euthanizedafter imaging and their organs harvested and analyzed for Fe content (Figure 5 B). The amount of Fe in the tumors of animals injectedwith the complete NPs was nearly double that found with nontargeted NPs or the nontreated controls.More interestingly, the Fe concentration values for the individual animals correlated well with thedecrease in signal from the T2 maps (Figure S11 A). Anincreased amount of Fe in organs such as the liver and spleen was also detected, an effect that istypically observed following the administration of IONP contrast agents.21 This increase was more evident when nontargeted NPs were used, a resultattributed to the fact that targeted NPs were more efficiently retained within the tumors(Figure S11 B).


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)

A) Results from the analyses of T2 maps from a series of spinecho images acquired with different TEs. Only the region of interest comprising thetumor was considered for the analyses. B) Iron concentrations in the different organsmeasured 48 h after the injection of targeted NPs. The results are expressed as the mean ofthree independent experiments ±the standard deviation. *=statisticallydifferent with p<0.05, S. Int=small intestine,L. Int=large intestine. Representative tumor T2 maps areshown from a series of spin echo images acquired with different TEs before (C) and4 h after (D) the intravenous injection of targeted NPs. Color bar scale in milliseconds.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: A) Results from the analyses of T2 maps from a series of spinecho images acquired with different TEs. Only the region of interest comprising thetumor was considered for the analyses. B) Iron concentrations in the different organsmeasured 48 h after the injection of targeted NPs. The results are expressed as the mean ofthree independent experiments ±the standard deviation. *=statisticallydifferent with p<0.05, S. Int=small intestine,L. Int=large intestine. Representative tumor T2 maps areshown from a series of spin echo images acquired with different TEs before (C) and4 h after (D) the intravenous injection of targeted NPs. Color bar scale in milliseconds.
Mentions: Next, mice bearing tumors were intravenously injected with a mixture of the two populations ofNPs in the same needle. Results from mice (n=3) injected with targeted IONPsrevealed that the T2 relaxation time of the entire tumor had decreasedby approximately 14 % at 4 h after injection (Figure 5 A,C,D). Control nontargeted NPs and saline injections didnot produce any significant change in tumor contrast after 4 h(ΔT2∼0.4 %). Signal measurements from thebody T2-w images showed a decrease in the ratio of liver-to-brain signalboth with targeted and control nontargeted NPs, thus confirming the accumulation of NPs in the liverarea (Figure S10 C,D). To corroborate the MRI findings, the animals were euthanizedafter imaging and their organs harvested and analyzed for Fe content (Figure 5 B). The amount of Fe in the tumors of animals injectedwith the complete NPs was nearly double that found with nontargeted NPs or the nontreated controls.More interestingly, the Fe concentration values for the individual animals correlated well with thedecrease in signal from the T2 maps (Figure S11 A). Anincreased amount of Fe in organs such as the liver and spleen was also detected, an effect that istypically observed following the administration of IONP contrast agents.21 This increase was more evident when nontargeted NPs were used, a resultattributed to the fact that targeted NPs were more efficiently retained within the tumors(Figure S11 B).

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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Related in: MedlinePlus