Makis Angelakeris

Learning from Nature to Improve the Heat Generation of Iron-Oxide Nanoparticles for Magnetic Hyperthermia Applications

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.

Self-assembled multifunctional Fe/MgO nanospheres for magnetic resonance imaging and hyperthermia

UNLABELLEDnA one-step process for the production of nanoparticles presenting advanced magnetic properties can be achieved using vapor condensation. In this article, we report on the fabrication of Fe particles covered by a uniform MgO epitaxial shell. MgO has a lower surface energy than Fe, which results in a core-shell crystal formation. The particles satisfy a few of technical requirements for the practical use in real clinics, such as a high biocompatibility in living cells in-vitro, an injection through blood vessels without any clothing problems in murine model, a high absorption rate for magnetic hyperthermia at small particle concentration, and the potential to be used as contrast agent in the field of diagnostic magnetic imaging. They are also able to be used in drug delivery and magnetic-activated cell sorting.nnnFROM THE CLINICAL EDITORnIn this paper, the authors report on the synthesis of Fe particles covered by a uniform MgO epitaxial shell resulting in a core-shell crystal formation. The particles are proven to be useful as contrast agents for magnetic resonance imaging and have the potential to be useful as heating mediators for cancer therapy through hyperthermia. They also might be used in drug delivery and magnetic-activated cell sorting.

Size and compositionally controlled manganese ferrite nanoparticles with enhanced magnetization

A facile solvothermal approach was used to synthesize stable, superparamagnetic manganese ferrite nanoparticles with relatively small sizes (<10xa0nm) and enhanced magnetic features. Tetraethylene glycol has been used in all the syntheses as a biocompatible and stabilizing agent. By varying the oxidation state of manganese precursor, Mn(acac)2 to Mn(acac)3, different sizes, 8 and 5xa0nm, of MnFe2O4 nanoparticles were obtained respectively, while by tailoring the synthetic conditions iron-rich Mn0.77Fe2.23O4 nanoparticles have been isolated with identical sizes and enhanced saturation magnetization. The magnetization values increased from 58.2 to 68.3xa0Am2/kg and from 53.3 to 60.2xa0Am2/kg for the nanoparticles of 8 and 5xa0nm, respectively. Blocking temperature (TB), ranging from 80 to 180xa0K, and anisotropy constant (Keff), ranging from 1.5xa0×xa0105 to 4.9xa0×xa0105xa0J/m3, were found higher for the iron-rich samples and associated with size and composition effects.

In-situ particles reorientation during magnetic hyperthermia application: Shape matters twice

Promising advances in nanomedicine such as magnetic hyperthermia rely on a precise control of the nanoparticle performance in the cellular environment. This constitutes a huge research challenge due to difficulties for achieving a remote control within the human body. Here we report on the significant double role of the shape of ellipsoidal magnetic nanoparticles (nanorods) subjected to an external AC magnetic field: first, the heat release is increased due to the additional shape anisotropy; second, the rods dynamically reorientate in the orthogonal direction to the AC field direction. Importantly, the heating performance and the directional orientation occur in synergy and can be easily controlled by changing the AC field treatment duration, thus opening the pathway to combined hyperthermic/mechanical nanoactuators for biomedicine. Preliminary studies demonstrate the high accumulation of nanorods into HeLa cells whereas viability analysis supports their low toxicity and the absence of apoptotic or necrotic cell death after 24 or 48u2009h of incubation.

A facile microwave synthetic route for ferrite nanoparticles with direct impact in magnetic particle hyperthermia

The application of ferrite magnetic nanoparticles (MNPs) in medicine finds its rapidly developing emphasis on heating mediators for magnetic hyperthermia, the ever-promising fourth leg of cancer treatment. Usage of MNPs depends largely on the preparation processes to select optimal conditions and effective routes to finely tailor MNPs. Microwave heating, instead of conventional heating offers nanocrystals at significantly enhanced rate and yield. In this work, a facile mass-production microwave hydrothermal synthetic approach was used to synthesize stable ferromagnetic manganese and cobalt ferrite nanoparticles with sizes smaller than 14 nm from metal acetylacetonates in the presence of octadecylamine. Prolonging the reaction time from 15 to 60 min, led to ferrites with improved crystallinity while the sizes are slight increased. The high crystallinity magnetic nanoparticles showed exceptional magnetic heating parameters. In vitro application was performed using the human osteosarcoma cell line Saos-2 incubated with manganese ferrite nanoparticles. Hyperthermia applied in a two cycle process, while AC magnetic field remained on until the upper limit of 45 °C was achieved. The comparative results of the AC hyperthermia efficiency of ferrite nanoparticles in combination with the in vitro study coincide with the magnetic features and their tunability may be further exploited for AC magnetic hyperthermia driven applications.

Structural and giant magnetoresistance characterization of AgCo multilayers

Abstract Ag Co multilayers were prepared on various substrates (Si, polyimide and glass) by e-beam evaporation under ultra high vacuum. X-ray diffraction and high resolution electron microscopy studies showed a deterioration of multilayer structure upon reducing the individual Co-layer thickness to 0.5 nm. Furthermore, the saturation field in the parallel field geometry increases, as SQUID magnetometry revealed, while magnetoresistance reaches 16% at room temperature and exceeds 30% at 30 K. Magnetoresistance values were found to depend strongly on individual layer thicknesses as well as on the total film thickness.

Tunable AC Magnetic Hyperthermia Efficiency of Ni Ferrite Nanoparticles

Nickel ferrite nanoparticles, with sizes lying within the superparamagnetic ferrimagnetic transition region, were synthesized using the solvothermal and the thermal decomposition method. Iron and nickel precursors as well as a variety of surfactants were used at adequate proportions to achieve structural and morphological, and hence magnetic tuning of the nanoparticles. X-ray diffraction and electron microscopy were used to visualize the actual particle size, morphology, and monodispersity aspects and to verify the obtained crystal structure. The magnetic hyperthermia response of nickel ferrite nanoparticles and the corresponding mechanisms of heating losses are studied in an effort to unravel the interconnections between the physical properties of magnetic nanoparticles and the tunable ac magnetic hyperthermia efficiency.

Influence of Pt-doping on structural, magnetic and magnetotransport properties of granular Ag-Co multilayers

Abstract The effect of Pt doping on the Ag layers of granular Ag-Co multilayers is studied. Studies performed via X-ray diffractometry and transmission electron microscopy reveal a structural transition of the samples from granular to multilayer form dependent on Pt concentration. Magnetic hysteresis appearance and magnetoresistance ratio reduction also support the structural transition.

Effect of low frequency magnetic fields on the growth of MNPs-treated HT29 colon cancer cells

Recent investigations have attempted to understand and exploit the impact of magnetic field-actuated internalized magnetic nanoparticles (MNPs) on the proliferation rate of cancer cells. Due to the complexity of the parameters governing magnetic field-exposure though, individual studies to date have raised contradictory results. In our approach we performed a comparative analysis of key parameters related to the cell exposure of cancer cells to magnetic field-actuated MNPs, and to the magnetic field, in order to better understand the factors affecting cellular responses to magnetic field-stimulated MNPs. We used magnetite MNPs with a hydrodynamic diameter of 100 nm and studied the proliferation rate of MNPs-treated versus untreated HT29 human colon cancer cells, exposed to either static or alternating low frequency magnetic fields with varying intensity (40-200 mT), frequency (0-8 Hz) and field gradient. All three parameters, field intensity, frequency, and field gradient affected the growth rate of cells, with or without internalized MNPs, as compared to control MNPs-untreated and magnetic field-untreated cells. We observed that the growth inhibitory effects induced by static and rotating magnetic fields were enhanced by pre-treating the cells with MNPs, while the growth promoting effects observed in alternating field-treated cells were weakened by MNPs. Compared to static, rotating magnetic fields of the same intensity induced a similar extend of cell growth inhibition, while alternating fields of varying intensity (70 or 100 mT) and frequency (0, 4 or 8 Hz) induced cell proliferation in a frequency-dependent manner. These results, highlighting the diverse effects of mode, intensity, and frequency of the magnetic field on cell growth, indicate that consistent and reproducible results can be achieved by controlling the complexity of the exposure of biological samples to MNPs and external magnetic fields, through monitoring crucial experimental parameters. We demonstrate that further research focusing on the accurate manipulation of the aforementioned magnetic field exposure parameters could lead to the development of successful non-invasive therapeutic anticancer approaches.

Size-selected Fe3O4–Au hybrid nanoparticles for improved magnetism-based theranostics

Size-selected Fe3O4–Au hybrid nanoparticles with diameters of 6–44 nm (Fe3O4) and 3–11 nm (Au) were prepared by high temperature, wet chemical synthesis. High-quality Fe3O4 nanocrystals with bulk-like magnetic behavior were obtained as confirmed by the presence of the Verwey transition. The 25 nm diameter Fe3O4–Au hybrid nanomaterial sample (in aqueous and agarose phantom systems) showed the best characteristics for application as contrast agents in magnetic resonance imaging and for local heating using magnetic particle hyperthermia. Due to the octahedral shape and the large saturation magnetization of the magnetite particles, we obtained an extraordinarily high r 2-relaxivity of 495 mM−1·s−1 along with a specific loss power of 617 W·gFe −1 and 327 W·gFe −1 for hyperthermia in aqueous and agarose systems, respectively. The functional in vitro hyperthermia test for the 4T1 mouse breast cancer cell line demonstrated 80% and 100% cell death for immediate exposure and after precultivation of the cells for 6 h with 25 nm Fe3O4–Au hybrid nanomaterials, respectively. This confirms that the improved magnetic properties of the bifunctional particles present a next step in magnetic-particle-based theranostics.