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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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T1W and T2W magnetic resonance images of Prussian blue and MnPB at 3 T.Abbreviations: T1W, T1-weighted; T2W, T2-weighted; MnPB, manganese-containing Prussian blue.
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f3-ijn-9-2581: T1W and T2W magnetic resonance images of Prussian blue and MnPB at 3 T.Abbreviations: T1W, T1-weighted; T2W, T2-weighted; MnPB, manganese-containing Prussian blue.

Mentions: We serially diluted Prussian blue and MnPB nano-particles to determine their longitudinal and transverse relaxivities (r1 and r2 values, respectively) at a magnetic field strength of 3 T (Figures 3 and S5). Relaxivity measurements with MnPB yielded an r value of 15.8 mM−1 s−1 and an r2 value of 143 mM−1 s−1. Similar measurements carried out with Prussian blue (without manganese) yielded an r1 value of 7.9 mM−1 s−1 and an r2 value of 14.4 mM−1 s−1. The r1 and r2 values for MnPB and Prussian blue are shown in Table 1.


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)

T1W and T2W magnetic resonance images of Prussian blue and MnPB at 3 T.Abbreviations: T1W, T1-weighted; T2W, T2-weighted; MnPB, manganese-containing Prussian blue.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-9-2581: T1W and T2W magnetic resonance images of Prussian blue and MnPB at 3 T.Abbreviations: T1W, T1-weighted; T2W, T2-weighted; MnPB, manganese-containing Prussian blue.
Mentions: We serially diluted Prussian blue and MnPB nano-particles to determine their longitudinal and transverse relaxivities (r1 and r2 values, respectively) at a magnetic field strength of 3 T (Figures 3 and S5). Relaxivity measurements with MnPB yielded an r value of 15.8 mM−1 s−1 and an r2 value of 143 mM−1 s−1. Similar measurements carried out with Prussian blue (without manganese) yielded an r1 value of 7.9 mM−1 s−1 and an r2 value of 14.4 mM−1 s−1. The r1 and r2 values for MnPB and Prussian blue are shown in Table 1.

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