In vitro cellular activity of maghemite/cerium oxide magnetic nanoparticles with antioxidant properties.

Magnetic γ-Fe2O3/CeO2 nanoparticles were obtained by precipitation of Ce(NO3)3 with ammonia in the presence of γ-Fe2O3 seeds. The formation of CeO2 nanoparticles on the seeds was confirmed by transmission electron microscopy linked with selected area electron diffraction, energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy, and dynamic light scattering. The γ-Fe2O3/CeO2 particle surface was functionalized with PEG-neridronate to improve the colloidal stability in PBS and biocompatibility. Chemical and in vitro biological assays proved that the nanoparticles, due to the presence of cerium oxide, effectively scavenged radicals, thus decreasing oxidative stress in the model cell line. PEG functionalization of the nanoparticles diminished their in vitro aggregation and facilitated lysosomal cargo degradation in cancer cells during autophagy, which resulted in concentration-dependent cytotoxicity of the nanoparticles. Finally, the iron oxide core allowed easy magnetic separation of the particles from liquid media and may enable monitoring of nanoparticle biodistribution in organisms using magnetic resonance imaging.

Cerium Oxide-Decorated γ-Fe2O3 Nanoparticles: Design, Synthesis and in vivo Effects on Parameters of Oxidative Stress.

Magnetic γ-Fe2O3/CeOx nanoparticles were obtained by basic coprecipitation/oxidation of iron chlorides with hydrogen peroxide, followed by precipitation of Ce(NO3)3 with ammonia. The appearance of CeOx on the magnetic particle surface was confirmed by X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), and elemental analysis; a magnetometer was used to measure the magnetic properties of γ-Fe2O3/CeOx. The relatively high saturation magnetization of the particles (41.1 A·m2/kg) enabled magnetic separation. The surface of γ-Fe2O3/CeOx particles was functionalized with PEG-neridronate of two different molecular weights to ensure colloidal stability and biocompatibility. The ability of the particles to affect oxidative stress in hereditary hypertriglyceridemic (HHTg) rats was tested by biological assay of the liver, kidney cortex, and brain tissues. An improvement was observed in both enzymatic [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] and non-enzymatic (reduced (GSH) and oxidized (GSSG) glutathione) levels of antioxidant defense and lipid peroxidation parameters [4-hydroxynonenal (4-HNE) and malondialdehyde (MDA)]. The results corresponded with chemical determination of antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, proving that in the animal model γ-Fe2O3/CeOx@PEG2,000 nanoparticles effectively scavenged radicals due to the presence of cerium oxide, in turn decreasing oxidative stress. These particles may therefore have the potential to reduce disorders associated with oxidative stress and inflammation.

The negative effect of magnetic nanoparticles with ascorbic acid on peritoneal macrophages.

Superparamagnetic iron oxide nanoparticles (SPIOn) are widely used as a contrast agent for cell labeling. Macrophages are the first line of defense of organisms in contact with nanoparticles after their administration. In this study we investigated the effect of silica-coated nanoparticles (γ-Fe2O3-SiO2) with or without modification by an ascorbic acid (γ-Fe2O3-SiO2-ASA), which is meant to act as an antioxidative agent on rat peritoneal macrophages. Both types of nanoparticles were phagocytosed by macrophages in large amounts as confirmed by transmission electron microscopy and Prusian blue staining, however they did not substantially affect the viability of exposed cells in monitored intervals. We further explored cytotoxic effects related to oxidative stress, which is frequently documented in cells exposed to nanoparticles. Our analysis of double strand breaks (DSBs) marker γH2AX showed an increased number of DSBs in cells treated with nanoparticles. Nanoparticle exposure further revealed only slight changes in the expression of genes involved in oxidative stress response. Lipid peroxidation, another marker of oxidative stress, was not significantly affirmed after nanoparticle exposure. Our data indicate that the effect of both types of nanoparticles on cell viability, or biomolecules such as DNA or lipids, was similar; however the presence of ascorbic acid, either bound to the nanoparticles or added to the cultivation medium, worsened the negative effect of nanoparticles in various tests performed. The attachment of ascorbic acid on the surface of nanoparticles did not have a protective effect against induced cytotoxicity, as expected.

Biological evaluation of surface-modified magnetic nanoparticles as a platform for colon cancer cell theranostics.

Magnetic nanoparticles offer multiple possibilities for biomedical applications. Besides their physico-chemical properties, nanoparticle-cellular interactions are determinant for biological safety. In this work, magnetic nanoparticles were synthesized by one-shot precipitation or two-step reaction and coated with biocompatible polymers, such as poly(l-lysine) and poly(N,N-dimethylacrylamide-co-acrylic acid), and carbohydrates, like l-ascorbic acid, d-galactose, d-mannose, and sucrose. The resulting magnetic nanoparticles were characterized by dynamic light scattering, FT-Raman spectroscopy, transmission electron microscopy, SQUID magnetometry, and Mössbauer spectroscopy. Ability of the nanoparticles to be used in theranostic applications was also evaluated, showing that coating with biocompatible polymers increased the heating efficiency. Nanoparticles synthesized by one-shot precipitation were 50% larger (∼13nm) than those obtained by a two-step reaction (∼8nm). Magnetic nanoparticles at concentrations up to 500µgmL-1 were non-cytotoxic to L929 fibroblasts. Particles synthesized by one-shot precipitation had little effect on viability, cell cycle and apoptosis of the three human colon cancer cell lines used: Caco-2, HT-29, and SW-480. At the same concentration (500µgmL-1), magnetic particles prepared by a two-step reaction reduced colon cancer cell viability by 20%, affecting cell cycle and inducing cell apoptosis. Uptake of surface-coated magnetic nanoparticles by colon cancer cells was dependent on particle synthesis, surface coating and incubation time.