In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting.

In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 µg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.

A new quantitative method to determine the uptake of SPIONs in animal tissue and its application to determine the quantity of nanoparticles in the liver and lung of Balb-c mice exposed to the SPIONs.

We propose a new method for determining the quantity of superparamagnetic iron oxide nanoparticles (Fe3O4, SPIONs) embedded in animal tissue using magnetization measurements. With this method, the smallest detectable quantity of magnetite nanoparticles in a tissue sample is -1 microg. We showed that this method has proved being efficient. In this study, we focused in determining the quantity of SPION confined in lung and liver tissue of mice injected with -13 nm magnetite superparamagnetic nanoparticles. Furthermore, the method allowed us to detect the magnetite nanoparticles present in animal tissues without letting the natural iron ions present in the tissue or blood interfere with the measurements.

Surface spin-glass freezing in interacting core-shell NiO nanoparticles.

Magnetization and AC susceptibility measurements have been performed on ∼3 nm NiO nanoparticles in powder form. The results indicate that the structure of the particles can be considered as consisting of an antiferromagnetically ordered core, with an uncompensated magnetic moment, and a magnetically disordered surface shell. The core magnetic moments block progressively with decreasing temperature, according to the distribution of their anisotropy energy barriers, as shown by a broad maximum of the low field zero-field-cooled magnetization (M(ZFC)) and in the in-phase component χ' of the AC susceptibility, centred at ∼70 K. On the other hand, surface spins thermally fluctuate and freeze in a disordered spin-glass-like state at much lower temperature, as shown by a peak in M(ZFC) (at 17 K, for H = 50 Oe) and in χ'. The temperature of the high temperature χ' peak changes with frequency according to the Arrhenius law; instead, for the low temperature maximum a power law dependence of the relaxation time was found, τ = τ(0)(T(g)/(T(ν)-T(g)))(α), where α = 8, like in spin glasses, τ(0) = 10(-12) s and T(g) = 15.9 K. The low temperature surface spin freezing is accompanied by a strong enhancement of magnetic anisotropy, as shown by the rapid increase of coercivity and high field susceptibility. Monte Carlo simulations for core/shell antiferromagnetic particles, with an antiferromagnetic core and a disordered shell, reproduce the qualitative behaviour of the temperature dependence of the coercivity. Interparticle interactions lead to a shift to a high temperature of the distribution of the core moment blocking temperature and to a reduction of magnetization dynamics.