title: Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors.
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.
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA.
authors.forename: Matthieu F
authors.initials: MF
authors.lastname: Dumont
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Yadavilli
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA ; Department of Radiology, George Washington University, Washington, DC, USA.
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Sze
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA ; Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.
authors.forename: Javad
authors.initials: J
authors.lastname: Nazarian
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA ; Department of Radiology, George Washington University, Washington, DC, USA ; Department of Pediatrics, George Washington University, Washington, DC, USA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D020295:Brain Stem Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005295:Ferrocyanides / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods; D009928:Organ Specificity; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005295:Ferrocyanides; D008345:Manganese; C000170:ferric ferrocyanide
keywords: Prussian blue; fluorescence; imaging; magnetic resonance imaging; manganese; multimodal; nanoparticles; pediatric brain tumors