Biofunctionalized Gadolinium-Containing Prussian Blue Nanoparticles as Multimodal\nMolecular Imaging Agents

Abstract

Molecular\nimaging agents enable the visualization of phenomena\nwith cellular and subcellular level resolutions and therefore have\nenormous potential in improving disease diagnosis and therapy assessment.\nIn this article, we describe the synthesis, characterization, and\ndemonstration of core–shell, biofunctionalized, gadolinium-containing\nPrussian blue nanoparticles as multimodal molecular imaging agents.\nOur multimodal nanoparticles combine the advantages of MRI and fluorescence.\nThe core of our nanoparticles consists of a Prussian blue lattice\nwith gadolinium ions located within the lattice interstices that confer\nhigh relaxivity to the nanoparticles providing MRI contrast. The relaxivities\nof our nanoparticles are nearly nine times those observed for the\nclinically used Magnevist. The nanoparticle MRI core is biofunctionalized\nwith a layer of fluorescently labeled avidin that enables fluorescence\nimaging. Biotinylated antibodies are attached to the surface avidin\nand confer molecular specificity to the nanoparticles by targeting\ncell-specific biomarkers. We demonstrate our nanoparticles as multimodal\nmolecular imaging agents in an <i>in vitro</i> model consisting\nof a mixture of eosinophilic cells and squamous epithelial cells.\nOur nanoparticles specifically detect eosinophilic cells and not squamous\nepithelial cells, via both fluorescence imaging and MRI <i>in\nvitro</i>. These results suggest the potential of our biofunctionalized\nPrussian blue nanoparticles as multimodal molecular imaging agents <i>in vivo</i>.