Disruptive chemical doping in a ferritin‐based iron oxide nanoparticle to decrease r 2 and enhance detection with T 1 ‐weighted MRI

Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity ( r 2 ). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r 2 . While sensitive, they can have limited in vivo detection due to a number of constraints with T 2 or T 2 *‐weighted imaging. T 1 ‐weighted imaging is often preferred for molecular MRI, but most T 1 ‐shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T 2 and limit the range of concentrations detectable with T 1 ‐weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un‐coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ±20 000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ±20 000 Oe. This tungsten–iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity ( r 1 ) of 4870 m m −1 s −1 and a reduced transverse relaxivity ( r 2 ) of 9076 m m −1 s −1 compared with native ferritin. The accumulation of the particles was detected with T 1 ‐weighted MRI in concentrations from 20 to 400 n m in vivo , both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 n m particle concentrations, making them potentially important for targeted molecular MRI. Copyright © 2014 John Wiley & Sons, Ltd.