Architectured design of superparamagnetic Fe3O4 nanoparticles for application as MRI contrast agents: mastering size and magnetism for enhanced relaxivity

Abstract

This work reports the mastered design of novel water-dispersible superparamagnetic iron oxide nanomaterials with enhanced magnetic properties and reduced size. A straightforward cost-effective aqueous coprecipitation route was developed, based on the use of three new coprecipitation agents: the polydentate bases diethanolamine, triethanolamine and triisopropanolamine. Through the selection of these alkanolamines which presented different complexing properties, an improvement of the surface spin order could be achieved upon the reduction of the nanomaterial dimensions (from 8.7 to 3.8 nm) owing to the complexation of the polydentate bases with the subcoordinated iron cations on the particle surface. In particular, the alkanolamine with the highest chelating ability (triethanolamine) led to the nanomaterial with the smallest size and the thinnest magnetic “dead” layer. In order to evaluate the importance of the dual control of size and magnetism, the relaxometric properties of the nanomaterials were investigated, whereby maximum values of transverse relaxivity r₂ of 300.30 and 253.92 mM⁻¹ s⁻¹ at 25 and 37 °C, respectively (at 20 MHz) were achieved, making these nanomaterials potential T₂-weighted MRI contrast agents. Moreover, these values were significantly higher than those reported for commercial T₂ contrast agents and other iron oxides with identical dimensions. Hence, we were able to demonstrate that the r₂ enhancement cannot only be achieved by an increase of particle/cluster size, but also through the precise control of the surface magnetic properties while constraining the nanomaterial dimensions. These achievements open up new perspectives on the mastered design of magnetic nanoprobes, overcoming the limitations related to the deleterious effect of size reduction.