Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy. This review provides a comprehensive description of the fundamental aspects of SPION formulation and highlights various recent approaches regarding in vivo applications in the field of cancer therapy.

Cobalt ferrite nanoparticles (CoFe₂O₄ NPs) were synthesized by coprecipitation followed by treatments with diluted nitric acid and sodium citrate. Transmission electron microscope (TEM) and photon correlation spectroscopy (PCS) characterization showed that the size distributions of these nanoparticles were monodisperse and that no aggregation occurred. This colloid showed a long‐term stability. Through adjustment of the concentrations of reactants and reaction temperature, the size of the NPs can be tuned from 6 to 80 nm. The size‐control mechanism is explained by a nucleation‐growth model, where the local concentration of monomers is assumed to decide the size of nuclei, and reaction temperatures influence the growth of nuclei. Magnetization and relaxivity r_1,2 measurements showed that the NPs revealed size‐dependent magnetization and relaxivity properties, which are explained via a “dead magnetic layer” theory where reductions of saturation magnetization (Ms) and r_1,2 are assumed to be caused by the demagnetization of surface spins.

This study reports the synthesis of stabilized ultrasmall iron oxide nanoparticles (USPIO) as bimodal probes for magnetic resonance and optical imaging. These nanosystems are based on small iron oxide cores surrounded by a thin polysiloxane shell exhibiting carboxylic acid functions. Thanks to these functions, hybrid particles were obtained by conjugating a fluorophore to the superparamagnetic contrastophore. Such modification allowed us to directly follow these USPIO in cellulo, which provided interesting information about their internalization pathway and cellular distribution upon mitosis. Finally, the efficiency of these systems as probes for bimodal imaging was emphasized by the observation of their in vivo behavior in mice using magnetic resonance and optical imaging.

This study reports the development of a continuous flow process enabling the synthesis of very small iron oxide nanoparticles (VSION) intended for T₁-weighted magnetic resonance imaging (MRI). The influence of parameters, such as the concentration/nature of surfactants, temperature, pressure and the residence time on the thermal decomposition of iron(III) acetylacetonate in organic media was evaluated. As observed by transmission electron microscopy (TEM), the diameter of the resulting nanoparticle remains constant when modifying the residence time. However, significant differences were observed in the magnetic and relaxometric studies. This continuous flow experimental setup allowed the production of VSION with high flow rates (up to 2 mL·min⁻¹), demonstrating the efficacy of such process compared to conventional batch procedure for the scale-up production of VSION.