Synthesis of Manganese Zinc Ferrite Nanoparticles in Medical-Grade Silicone for MRI Applications.

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study's temperature range. Embedded nanoparticles did not influence spin-lattice relaxation, but they shorten the longer component of spin-spin nuclear relaxation times of silicone's protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s-1 mmol-1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro-silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).

Tailoring cellular microenvironments using scaffolds based on magnetically-responsive polymer brushes.

A variety of polymeric scaffolds with the ability to control cell detachment has been created for cell culture using stimuli-responsive polymers. However, the widely studied and commonly used thermo-responsive polymeric substrates always affect the properties of the cultured cells due to the temperature stimulus. Here, we present a different stimuli-responsive approach based on poly(3-acrylamidopropyl)trimethylammonium chloride) (poly(APTAC)) brushes with homogeneously embedded superparamagnetic iron oxide nanoparticles (SPIONs). Neuroblastoma cell detachment was triggered by an external magnetic field, enabling a non-invasive process of controlled transfer into a new place without additional mechanical scratching and chemical/biochemical compound treatment. Hybrid scaffolds obtained in simultaneous surface-initiated atom transfer radical polymerization (SI-ATRP) were characterized by atomic force microscopy (AFM) working in the magnetic mode, secondary ion mass spectrometry (SIMS), and X-ray photoelectron spectroscopy (XPS) to confirm the magnetic properties and chemical structure. Moreover, neuroblastoma cells were cultured and characterized before and after exposure to a neodymium magnet. Controlled cell transfer triggered by a magnetic field is presented here as well.

Selective magnetometry of superparamagnetic iron oxide nanoparticles in liquids.

We show that the properties of superparamagnetic iron oxide nanoparticles suspended in liquids can be effectively studied using Magnetic Circular Dichroism in Resonant Inelastic X-ray Scattering. Analysis of the spectral shape and magnetic contrast produced by this experiment enables an assessment of the site distribution and magnetic state of metal ions in the spinel phase. The selective magnetization profile of particles as derived from the field dependence of dichroism empowers an estimation of particle size distribution. Furthermore, the new proposed methodology discriminates sizes that are below the detection limits of X-ray and light scattering probes and that are difficult to spot in TEM.

Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin.

BACKGROUND: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. METHOD: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. RESULTS: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. CONCLUSION: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.

A Hybrid System for Magnetic Hyperthermia and Drug Delivery: SPION Functionalized by Curcumin Conjugate.

Cancer is among the leading causes of death worldwide, thus there is a constant demand for new solutions, which may increase the effectiveness of anti-cancer therapies. We have designed and successfully obtained a novel, bifunctional, hybrid system composed of colloidally stabilized superparamagnetic iron oxide nanoparticles (SPION) and curcumin containing water-soluble conjugate with potential application in anticancer hyperthermia and as nanocarriers of curcumin. The obtained nanoparticulate system was thoroughly studied in respect to the size, morphology, surface charge, magnetic properties as well as some biological functions. The results revealed that the obtained nanoparticles, ca. 50 nm in diameter, were the agglomerates of primary particles with the magnetic, iron oxide cores of ca. 13 nm, separated by a thin layer of the applied cationic derivative of chitosan. These agglomerates were further coated with a thin layer of the sodium alginate conjugate of curcumin and the presence of both polymers was confirmed using thermogravimetry. The system was also proven to be applicable in magnetic hyperthermia induced by the oscillating magnetic field. A high specific absorption rate (SAR) of 280 [W/g] was registered. The nanoparticles were shown to be effectively uptaken by model cells. They were found also to be nontoxic in the therapeutically relevant concentration in in vitro studies. The obtained results indicate the high application potential of the new hybrid system in combination of magnetic hyperthermia with delivery of curcumin active agent.

Biocompatible and fluorescent superparamagnetic iron oxide nanoparticles with superior magnetic properties coated with charged polysaccharide derivatives.

Syntheses and characterizations of biocompatible superparamagnetic iron oxide nanoparticles with embedded curcumin and coated with ultrathin layer of hyaluronic acid-curcumin (HA-Cur) conjugate have been reported. Zeta potential measurements confirmed effective coating of native iron oxide nanoparticles stabilized by cationic derivative of chitosan (SPION-CCh) with the synthesized HA-Cur conjugate. Both SPIONs with embedded curcumin and the ones coated with HA-Cur (SPION-CCh/HA-Cur) revealed desired magnetic characteristics while fluorescent properties were much better for the coated nanoparticles. SPION-CCh/HA-Cur nanoparticles were shown to be very promising candidates for T2 MRI contrast agents as they can easily penetrate cell membrane and their relaxivity is exceptionally high (ca. 470mM-1s-1). They may be also tracked using confocal fluorescence microscopy due to the presence of fluorescent curcumin in the coating. In vitro studies indicated that the obtained SPIONs-CCh/HA-Cur were non-toxic for EA.hy926 endothelial cells.