Iron Oxide Nanoparticles for Biomedical Applications: Synthesis, Functionalization, and Application

Abstract Because of their unique magnetic properties, nontoxicity, and biodegradability, superparamagnetic iron oxide nanoparticles (IONPs) have been increasingly employed in magnetic resonance imaging (MRI), targeted drug delivery, therapy, and cell separation. One current challenge for iron oxide-based NPs is the design of NPs that is able to combine in one nanoobject both magnetic hyperthermia (MH) and MRI with the best efficiency in order to reduce the dose injected in the patient. Ultrasmall iron oxide NPs are already commercially used as T 2 contrast agent for MRI. The use of MH as a stand-alone or an adjacent therapy for cancer is closer to be a reality in every hospital thanks to the positive results achieved by the clinical trials carried out by Magforce (Germany). Nonetheless, the need for direct intratumoral injection of large amounts of NPs to achieve a therapeutic effect only points out at the need of improving the available nanomaterials for MH. Different parameters may be varied to increase the effective heat loss of a ferrofluid such as size, shape anisotropy, or composition. In all these applications, the tailoring of the NP surface is mandatory not only to improve biocompatibility, solubility, and stability but also to ensure a small particle size distribution (below 100 nm) after decoration and to preserve good magnetic properties, for example, a high saturation magnetization. Furthermore, the nature of coating and the hydrodynamic size can affect the fate of NPs in biological system, such as cellular uptake and accumulation, circulation, and clearance from the body. Moreover, appropriate surface functionality is the perquisite for conjugating biomolecules to NPs for biomedical applications. In that context, the main challenges in the design of iron oxide NPs for MRI and magnetic hyperthermia properties are explained, and the main NP synthesis methods and the main molecules and functionalization methods are described.