The influence of cation incorporation and leaching in the properties of Mn-doped nanoparticles for biomedical applications.

HYPOTHESIS: Superparamagnetic MnxFe3-xO4 nanoparticles are promising materials for applications in biomedicine and other fields. Small variations in the Mn/Fe ratio have a strong impact on the properties of the nanoparticles. Those variations may be caused by the synthesis itself and by common post-synthesis manipulations like surface modification. EXPERIMENTS: Mn-ferrite nanoparticles have been prepared changing systematically the Mn/Fe ratio of the metal precursors and repeating each reaction three times. Nanoparticles were subjected to surface modification with two different and typical molecules to stabilize them in aqueous media. The discrepancy in the Mn/Fe ratios of the precursors with the ones measured after the synthesis and the surface modification have been studied, as well as its impact on the saturation magnetization, blocking temperature, contrast enhancement for magnetic resonance imaging, magnetic heating, and on the cytotoxicity. FINDINGS: Mn is incorporated in the nanoparticles in a relatively lower amount than Fe and, as this report shows for the first time, both Mn and Fe ions leach out from the nanoparticles during the surface modification step. The blocking temperature decreases exponentially as the Mn/Fe ratio increases. The transverse and longitudinal relaxation times and the magnetic heating ability change appreciably even with small variations in the composition.

Tailor-made PEG coated iron oxide nanoparticles as contrast agents for long lasting magnetic resonance molecular imaging of solid cancers.

Magnetic resonance imaging (MRI) is the most powerful technique for non-invasive diagnosis of human diseases and disorders. Properly designed contrast agents can be accumulated in the damaged zone and be internalized by cells, becoming interesting cellular MRI probes for disease tracking and monitoring. However, this approach is sometimes limited by the relaxation rates of contrast agents currently in clinical use, which show neither optimal pharmacokinetic parameters nor toxicity. In this work, a suitable contrast agent candidate, based on iron oxide nanoparticles (IONPs) coated with polyethyleneglycol, was finely designed, prepared and fully characterized under a physical, chemical and biological point of view. To stand out the real potential of our study, all the experiments were performed in comparison with Ferumoxytol, a FDA approved IONPs. IONPs with a core size of 15 nm and coated with polyethyleneglycol of 5 kDa (OD15-P5) resulted the best ones, being able to be uptaken by both tumoral cells and macrophages and showing no toxicity for in vitro and in vivo experiments. In vitro and in vivo MRI results for OD15-P5 showed r2 relaxivity values higher than Ferumoxitol. Furthermore, the injected OD15-P5 were completely retained at the tumor site for up to 24 h showing high potential as MRI contrast agents for real time long-lasting monitoring of the tumor evolution.