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Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors.

Dumont MF, Yadavilli S, Sze RW, Nazarian J, Fernandes R - Int J Nanomedicine (2014)

Bottom Line: Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs.We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles.Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro.

View Article: PubMed Central - PubMed

Affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA.

ABSTRACT
Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn(2+) ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling fluorescence imaging and functioning as a platform for the attachment of biotinylated ligands that target PBTs. The surfaces of our nanoparticles are modified with biotinylated antibodies targeting neuron-glial antigen 2 or biotinylated transferrin. Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs. We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles. Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro. Finally, we demonstrate the potential of these nanoparticles as PBT imaging agents by measuring their organ and brain biodistribution in an orthotopic mouse model of PBTs using ex vivo fluorescence imaging.

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Histological analysis of fluorescence-positive regions of mice brains with PBTs.Notes: (A) Sagittal slice of mouse brain stained with hematoxylin and eosin. (B) Inset showing a fluorescence image of the brain, with arrow indicating the viewing direction of the sagittal section in (A). (C, D) Progressive zooms of the hematoxylin and eosin-stained sagittal brain sections containing a hypercellular ventricular and periventricular region within the fluorescence-positive region.Abbreviation: PBT, pediatric brain tumor.
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f9-ijn-9-2581: Histological analysis of fluorescence-positive regions of mice brains with PBTs.Notes: (A) Sagittal slice of mouse brain stained with hematoxylin and eosin. (B) Inset showing a fluorescence image of the brain, with arrow indicating the viewing direction of the sagittal section in (A). (C, D) Progressive zooms of the hematoxylin and eosin-stained sagittal brain sections containing a hypercellular ventricular and periventricular region within the fluorescence-positive region.Abbreviation: PBT, pediatric brain tumor.

Mentions: Fluorescence measurements of the brains of the mice detected the nanoparticles in the brain between one hour and 3 hours, with the fluorescent signal reaching a maximum at one hour (Figure 8A). Little to no fluorescence was detected after 3 hours and in the control mouse brain (without nanoparticle injection). Fluorescence organ biodistribution measurements showed that the nanoparticles were cleared via the liver, kidney, and spleen (Figure 8B and 8C). Mouse brains that were positive for fluorescent signal were analyzed by histology. Sagittal sections of the brain stained by hematoxylin and eosin revealed a hypercellular region located within the fluorescently active brain segment localized in the ventricular and periventricular regions of the mouse brain (Figure 9). These results indicated the feasibility of utilizing our nanoparticles for fluorescence imaging of PBTs in vivo.


Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors.

Dumont MF, Yadavilli S, Sze RW, Nazarian J, Fernandes R - Int J Nanomedicine (2014)

Histological analysis of fluorescence-positive regions of mice brains with PBTs.Notes: (A) Sagittal slice of mouse brain stained with hematoxylin and eosin. (B) Inset showing a fluorescence image of the brain, with arrow indicating the viewing direction of the sagittal section in (A). (C, D) Progressive zooms of the hematoxylin and eosin-stained sagittal brain sections containing a hypercellular ventricular and periventricular region within the fluorescence-positive region.Abbreviation: PBT, pediatric brain tumor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043710&req=5

f9-ijn-9-2581: Histological analysis of fluorescence-positive regions of mice brains with PBTs.Notes: (A) Sagittal slice of mouse brain stained with hematoxylin and eosin. (B) Inset showing a fluorescence image of the brain, with arrow indicating the viewing direction of the sagittal section in (A). (C, D) Progressive zooms of the hematoxylin and eosin-stained sagittal brain sections containing a hypercellular ventricular and periventricular region within the fluorescence-positive region.Abbreviation: PBT, pediatric brain tumor.
Mentions: Fluorescence measurements of the brains of the mice detected the nanoparticles in the brain between one hour and 3 hours, with the fluorescent signal reaching a maximum at one hour (Figure 8A). Little to no fluorescence was detected after 3 hours and in the control mouse brain (without nanoparticle injection). Fluorescence organ biodistribution measurements showed that the nanoparticles were cleared via the liver, kidney, and spleen (Figure 8B and 8C). Mouse brains that were positive for fluorescent signal were analyzed by histology. Sagittal sections of the brain stained by hematoxylin and eosin revealed a hypercellular region located within the fluorescently active brain segment localized in the ventricular and periventricular regions of the mouse brain (Figure 9). These results indicated the feasibility of utilizing our nanoparticles for fluorescence imaging of PBTs in vivo.

Bottom Line: Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs.We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles.Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro.

View Article: PubMed Central - PubMed

Affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA.

ABSTRACT
Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn(2+) ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling fluorescence imaging and functioning as a platform for the attachment of biotinylated ligands that target PBTs. The surfaces of our nanoparticles are modified with biotinylated antibodies targeting neuron-glial antigen 2 or biotinylated transferrin. Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs. We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles. Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro. Finally, we demonstrate the potential of these nanoparticles as PBT imaging agents by measuring their organ and brain biodistribution in an orthotopic mouse model of PBTs using ex vivo fluorescence imaging.

Show MeSH
Related in: MedlinePlus