Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors

Abstract

Matthieu F Dumont,1 Sridevi Yadavilli,2 Raymond W Sze,1,4 Javad Nazarian,2,3 Rohan Fernandes1,4,5 1Sheikh Zayed Institute for Pediatric Surgical Innovation, 2Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC, USA; 3Department of Integrative Systems Biology, 4Department of Radiology, 5Department of Pediatrics, George Washington University, 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 Mn2+ 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. Keywords: Prussian blue, nanoparticles, imaging, pediatric brain tumors, fluorescence, magnetic resonance imaging, manganese, multimodal