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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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Properties of the MnPB nanoparticles.Notes: (A) Representative transmission electron microscopy image of MnPB nanoparticles. (B) Fourier transform infrared spectra of Prussian blue without interstitial manganese (solid line) and MnPB (dashed line) in the cyanide stretching region (1,900 cm−1 to 2,200 cm−1).Abbreviation: MnPB, manganese-containing Prussian blue.
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f2-ijn-9-2581: Properties of the MnPB nanoparticles.Notes: (A) Representative transmission electron microscopy image of MnPB nanoparticles. (B) Fourier transform infrared spectra of Prussian blue without interstitial manganese (solid line) and MnPB (dashed line) in the cyanide stretching region (1,900 cm−1 to 2,200 cm−1).Abbreviation: MnPB, manganese-containing Prussian blue.

Mentions: The MnPB nanoparticles were prepared using a single-pot, aqueous phase synthesis by addition of iron (II) chloride to a mixture containing manganese chloride and potassium hexacyanoferrate (III). The resulting MnPB nanoparticles had a mean size of 33±7 nm, measured using high-resolution TEM (Figures 2A and S1), and the nanoparticle lattice parameters corresponded to Prussian blue measured by selected area electron diffraction patterns (Figure S2). FTIR spectral measurements of the MnPB nanoparticles yielded a broad band at 2,070 cm−1, corresponding to the FeII–CN–FeIII cyanide stretch energy that was also obtained in the spectrum of Prussian blue (without manganese; Figure 2B). The FTIR spectrum for MnPB did not display a band at 2,149 cm−1 characteristic of MnII–NC–FeIII.44


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)

Properties of the MnPB nanoparticles.Notes: (A) Representative transmission electron microscopy image of MnPB nanoparticles. (B) Fourier transform infrared spectra of Prussian blue without interstitial manganese (solid line) and MnPB (dashed line) in the cyanide stretching region (1,900 cm−1 to 2,200 cm−1).Abbreviation: MnPB, manganese-containing Prussian blue.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-9-2581: Properties of the MnPB nanoparticles.Notes: (A) Representative transmission electron microscopy image of MnPB nanoparticles. (B) Fourier transform infrared spectra of Prussian blue without interstitial manganese (solid line) and MnPB (dashed line) in the cyanide stretching region (1,900 cm−1 to 2,200 cm−1).Abbreviation: MnPB, manganese-containing Prussian blue.
Mentions: The MnPB nanoparticles were prepared using a single-pot, aqueous phase synthesis by addition of iron (II) chloride to a mixture containing manganese chloride and potassium hexacyanoferrate (III). The resulting MnPB nanoparticles had a mean size of 33±7 nm, measured using high-resolution TEM (Figures 2A and S1), and the nanoparticle lattice parameters corresponded to Prussian blue measured by selected area electron diffraction patterns (Figure S2). FTIR spectral measurements of the MnPB nanoparticles yielded a broad band at 2,070 cm−1, corresponding to the FeII–CN–FeIII cyanide stretch energy that was also obtained in the spectrum of Prussian blue (without manganese; Figure 2B). The FTIR spectrum for MnPB did not display a band at 2,149 cm−1 characteristic of MnII–NC–FeIII.44

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