Iron oxide nanoparticles are widely used for biological applications thanks to their outstanding balance between magnetic properties, surface-to-volume ratio suitable for efficient functionalization and proven biocompatibility. Their development for MRI or magnetic particle hyperthermia concentrates much of the attention as these nanomaterials are already used within the health system as contrast agents and heating mediators. As such, the constant improvement and development for better and more reliable materials is of key importance. On this basis, this review aims to cover the rational design of iron oxide nanoparticles to be used as MRI contrast agents or heating mediators in magnetic hyperthermia, and reviews the state of the art of their use as nanomedicine tools.

Iron oxide nanoparticles are widely used as a contrast agent in magnetic resonance imaging (MRI), and may be used as therapeutic agent for magnetic hyperthermia if they display in particular high magnetic anisotropy. Considering the effect of nanoparticles shape on anisotropy, a reproducible shape control of nanoparticles is a current synthesis challenge. By investigating reaction parameters, such as the iron precursor structure, its water content, but also the amount of the surfactant (sodium oleate) reported to control the shape, iron oxide nanoparticles with different shape and composition were obtained, in particular, iron oxide nanoplates. The effect of the surfactant coming from precursor was taking into account by using in house iron stearates bearing either two or three stearate chains and the negative effect of water on shape was confirmed by considering these precursors after their dehydration. Iron stearates with three chains in presence of a ratio sodium oleate/oleic acid 1:1 led mainly to nanocubes presenting a core-shell Fe_1−xO@Fe_3−xO₄ composition. Nanocubes with straight faces were only obtained with dehydrated precursors. Meanwhile, iron stearates with two chains led preferentially to the formation of nanoplates with a ratio sodium oleate/oleic acid 4:1. The rarely reported flat shape of the plates was confirmed with 3D transmission electronic microscopy (TEM) tomography. The investigation of the synthesis mechanisms confirmed the major role of chelating ligand and of the heating rate to drive the cubic shape of nanoparticles and showed that the nanoplate formation would depend mainly on the nucleation step and possibly on the presence of a given ratio of oleic acid and chelating ligand (oleate and/or stearate).

Aqueous suspensions of dendronized iron oxide nanoparticles (NPs) have been obtained after functionalization, with two types of dendrons, of NPs synthesized either by coprecipitation (leading to naked NPs in water) or by thermal decomposition (NPs in situ coated by oleic acid in an organic solvent). Different grafting strategies have been optimized depending on the NPs synthetic method. The size distribution, the colloidal stability in isoosmolar media, the surface complex nature as well as the preliminary biokinetic studies performed with optical imaging, and the contrast enhancement properties evaluated through in vitro and in vivo MRI experiments, have been compared as a function of the nature of both dendrons and NPs. All functionalized NPs displayed good colloidal stability in water, however the ones bearing a peripheral carboxylic acid function gave the best results in isoosmolar media. Whereas the grafting rates were similar, the nature of the surface complex depended on the NPs synthetic method. The in vitro contrast enhancement properties were better than commercial products, with a better performance of the NPs synthesized by coprecipitation. On the other hand, the NPs synthesized by thermal decomposition were more efficient in vivo. Furthermore, they both displayed good biodistribution with renal and hepatobiliary elimination pathways and no consistent RES uptake.