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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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Manganese-containing Prussian blue nanoparticles for imaging of PBTs.Notes: (A) Schematic representation of manganese-containing Prussian blue nanoparticles comprised of an inorganic core that provides MRI contrast and a biofunctionalized shell consisting of fluorescently-labeled avidin and biotinylated PBT-targeting ligands. (B) Schematic representation of the Prussian blue lattice (ball and stick) containing interstitial Mn2+ and K+ ions.Abbreviations: ANG2, anti-neuron-glial antigen 2; MRI, magnetic resonance imaging; PBT, pediatric brain tumor.
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f1-ijn-9-2581: Manganese-containing Prussian blue nanoparticles for imaging of PBTs.Notes: (A) Schematic representation of manganese-containing Prussian blue nanoparticles comprised of an inorganic core that provides MRI contrast and a biofunctionalized shell consisting of fluorescently-labeled avidin and biotinylated PBT-targeting ligands. (B) Schematic representation of the Prussian blue lattice (ball and stick) containing interstitial Mn2+ and K+ ions.Abbreviations: ANG2, anti-neuron-glial antigen 2; MRI, magnetic resonance imaging; PBT, pediatric brain tumor.

Mentions: To generate nanoparticles suitable for imaging PBTs, we have synthesized MnPB nanoparticles with a core-shell design (Figure 1A). The Prussian blue nanoparticle core (iron [III] hexacyanoferrate [II]) has a permeable lattice structure and the ability to incorporate and retain metal ions for charge balance (Figure 1B). On account of this metal-binding ability, Prussian blue, a material approved by the US Food and Drug Administration and sold as Radiogardase™ (Heyltex Corporation, Katy, TX, USA),24 has been used by first responders in the event of a radiological emergency to sequester and promptly eliminate radioactive isotopes of cesium and thallium from the body.25,26 For the purpose of MRI, we can harness this metal-binding ability of Prussian blue to sequester paramagnetic Mn2+ ions within its lattice, thereby generating MRI contrast. We use manganese ions in the nanoparticles to mitigate safety concerns associated with gadolinium ions (Gd3+, typically used in commercial contrast agents) that have been linked to nephrogenic systemic fibrosis in patients with impaired renal function.27–30


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)

Manganese-containing Prussian blue nanoparticles for imaging of PBTs.Notes: (A) Schematic representation of manganese-containing Prussian blue nanoparticles comprised of an inorganic core that provides MRI contrast and a biofunctionalized shell consisting of fluorescently-labeled avidin and biotinylated PBT-targeting ligands. (B) Schematic representation of the Prussian blue lattice (ball and stick) containing interstitial Mn2+ and K+ ions.Abbreviations: ANG2, anti-neuron-glial antigen 2; MRI, magnetic resonance imaging; PBT, pediatric brain tumor.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-9-2581: Manganese-containing Prussian blue nanoparticles for imaging of PBTs.Notes: (A) Schematic representation of manganese-containing Prussian blue nanoparticles comprised of an inorganic core that provides MRI contrast and a biofunctionalized shell consisting of fluorescently-labeled avidin and biotinylated PBT-targeting ligands. (B) Schematic representation of the Prussian blue lattice (ball and stick) containing interstitial Mn2+ and K+ ions.Abbreviations: ANG2, anti-neuron-glial antigen 2; MRI, magnetic resonance imaging; PBT, pediatric brain tumor.
Mentions: To generate nanoparticles suitable for imaging PBTs, we have synthesized MnPB nanoparticles with a core-shell design (Figure 1A). The Prussian blue nanoparticle core (iron [III] hexacyanoferrate [II]) has a permeable lattice structure and the ability to incorporate and retain metal ions for charge balance (Figure 1B). On account of this metal-binding ability, Prussian blue, a material approved by the US Food and Drug Administration and sold as Radiogardase™ (Heyltex Corporation, Katy, TX, USA),24 has been used by first responders in the event of a radiological emergency to sequester and promptly eliminate radioactive isotopes of cesium and thallium from the body.25,26 For the purpose of MRI, we can harness this metal-binding ability of Prussian blue to sequester paramagnetic Mn2+ ions within its lattice, thereby generating MRI contrast. We use manganese ions in the nanoparticles to mitigate safety concerns associated with gadolinium ions (Gd3+, typically used in commercial contrast agents) that have been linked to nephrogenic systemic fibrosis in patients with impaired renal function.27–30

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