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Biofunctionalized Prussian Blue Nanoparticles for Multimodal Molecular Imaging Applications
Published on: April 28, 2015
Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors
Matthieu F Dumont1, Sridevi Yadavilli2, Raymond W Sze3
1Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA.
Insights
New manganese-containing Prussian blue nanoparticles offer dual MRI and fluorescence imaging for pediatric brain tumors (PBTs). These targeted agents show promise for monitoring PBTs and improving patient outcomes.
Area of Science:
- Nanotechnology
- Biomedical Imaging
- Oncology
Background:
- Pediatric brain tumors (PBTs) are a significant cause of childhood mortality.
- Effective monitoring of PBTs requires advanced imaging techniques.
- Current imaging methods lack the molecular specificity needed for precise disease tracking.
Purpose of the Study:
- To develop novel molecularly-specific imaging agents for pediatric brain tumors.
- To create multimodal nanoparticles for simultaneous magnetic resonance imaging (MRI) and fluorescence imaging.
- To evaluate the potential of these nanoparticles in preclinical models of PBTs.
Main Methods:
- Synthesis and characterization of manganese-containing Prussian blue nanoparticles with a core-shell structure.
- Biofunctionalization of nanoparticles with avidin for fluorescence imaging and targeted ligand attachment.
- Modification of nanoparticle surfaces with biotinylated antibodies targeting neuron-glial antigen 2 or transferrin.
- In vitro assessment of MRI and fluorescence imaging capabilities.
- Ex vivo biodistribution studies in an orthotopic mouse model of PBTs.
Main Results:
- Successfully synthesized and characterized multimodal manganese-containing Prussian blue nanoparticles.
- Demonstrated dual-mode MRI (positive and negative contrast) and fluorescence imaging capabilities in vitro.
- Confirmed overexpression of neuron-glial antigen 2 and transferrin receptor on PBTs.
- Validated nanoparticle targeting and imaging potential in a preclinical PBT model.
Conclusions:
- Manganese-containing Prussian blue nanoparticles are effective multimodal imaging agents for PBTs.
- These nanoparticles can be functionalized to target specific PBT biomarkers.
- The developed agents hold significant potential for improved PBT diagnosis, monitoring, and treatment response assessment.
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.

