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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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Fluorescence-based detection of PBT cells using biofunctionalized Prussian blue nanoparticles.Notes: Fluorescent image of BSG D10 treated with control nanoparticles, ie, (A) MnPB-A488 and (B) MnPB-A488-AbC, and experimental nanoparticles, ie, (C) MnPB-A488-ANG2. The green fluorescence comes from A488 on the constructs. Scale bars represent 20 μm.Abbreviations: BSG, brainstem glioma; MnPB, manganese-containing Prussian blue; A488, avidin-Alexa Fluor 488; ANG2, anti-neuron-glial antigen 2; AbC, eotaxin antibody; PBT, pediatric brain tumor.
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f6-ijn-9-2581: Fluorescence-based detection of PBT cells using biofunctionalized Prussian blue nanoparticles.Notes: Fluorescent image of BSG D10 treated with control nanoparticles, ie, (A) MnPB-A488 and (B) MnPB-A488-AbC, and experimental nanoparticles, ie, (C) MnPB-A488-ANG2. The green fluorescence comes from A488 on the constructs. Scale bars represent 20 μm.Abbreviations: BSG, brainstem glioma; MnPB, manganese-containing Prussian blue; A488, avidin-Alexa Fluor 488; ANG2, anti-neuron-glial antigen 2; AbC, eotaxin antibody; PBT, pediatric brain tumor.

Mentions: To investigate our nanoparticles as fluorescence imaging agents, we added fixed amounts of MnPB-A488-ANG2 (containing ANG2 antibody), MnPB-A488-AbC (with control antibody AbC), and MnPB-A488 (no antibody) to BSG D10 cells. Confocal fluorescence microscopy demonstrated that the MnPB-A488-ANG2 specifically targeted BSG D10 cells (Figure 6). Control (MnPB-A488-AbC and MnPB-A488) nanoparticles showed negligible binding to BSG D10 (negligible green fluorescence; Figure 6A and 6B).


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)

Fluorescence-based detection of PBT cells using biofunctionalized Prussian blue nanoparticles.Notes: Fluorescent image of BSG D10 treated with control nanoparticles, ie, (A) MnPB-A488 and (B) MnPB-A488-AbC, and experimental nanoparticles, ie, (C) MnPB-A488-ANG2. The green fluorescence comes from A488 on the constructs. Scale bars represent 20 μm.Abbreviations: BSG, brainstem glioma; MnPB, manganese-containing Prussian blue; A488, avidin-Alexa Fluor 488; ANG2, anti-neuron-glial antigen 2; AbC, eotaxin antibody; PBT, pediatric brain tumor.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ijn-9-2581: Fluorescence-based detection of PBT cells using biofunctionalized Prussian blue nanoparticles.Notes: Fluorescent image of BSG D10 treated with control nanoparticles, ie, (A) MnPB-A488 and (B) MnPB-A488-AbC, and experimental nanoparticles, ie, (C) MnPB-A488-ANG2. The green fluorescence comes from A488 on the constructs. Scale bars represent 20 μm.Abbreviations: BSG, brainstem glioma; MnPB, manganese-containing Prussian blue; A488, avidin-Alexa Fluor 488; ANG2, anti-neuron-glial antigen 2; AbC, eotaxin antibody; PBT, pediatric brain tumor.
Mentions: To investigate our nanoparticles as fluorescence imaging agents, we added fixed amounts of MnPB-A488-ANG2 (containing ANG2 antibody), MnPB-A488-AbC (with control antibody AbC), and MnPB-A488 (no antibody) to BSG D10 cells. Confocal fluorescence microscopy demonstrated that the MnPB-A488-ANG2 specifically targeted BSG D10 cells (Figure 6). Control (MnPB-A488-AbC and MnPB-A488) nanoparticles showed negligible binding to BSG D10 (negligible green fluorescence; Figure 6A and 6B).

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