Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance imaging

Magnetoferritin nanoparticles have been developed as high-relaxivity, functional contrast agents for MRI. Several previous techniques have relied on unloading native ferritin and re-incorporation of iron into the core, often resulting in a polydisperse sample. Here, a simplified technique is developed using commercially available horse spleen apoferritin to create monodisperse magnetoferritin. Iron oxide atoms were incorporated into the protein core via a step-wise Fe(II)Chloride addition to the protein solution under low O(2) conditions; subsequent filtration steps allow for separation of completely filled and superparamagnetic magnetoferritin from the partially filled ferritin. This method yields a monodisperse and homogenous solution of spherical particles with magnetic properties that can be used for molecular magnetic resonance imaging. With a transverse per-iron and per-particle relaxivity of 78 mM(-1) sec(-1) and 404,045 mM(-1) sec(-1), respectively, it is possible to detect ∼ 10 nM nanoparticle concentrations in vivo.