Control of physical properties in BiFeO3nanoparticles via Sm3+and Co2+ion doping.

Highly crystalline BiFeO3(BFO), Bi0.97Sm0.03FeO3(Sm-BFO) and BiFe0.97Co0.03O3(Co-BFO) nanoparticles (NPs) were utilized as potential magnetic hyperthermia agents at two different frequencies in the radiofrequency (RF) range, and the effect of Sm3+and Co2+ion doping on the physical properties of the material was examined. The thermal behaviour of the as-prepared powders disclosed that the crystallization temperature of the powders is affected by the incorporation of the dopants into the BFO lattice and the Curie transition temperature is decreased upon doping. Vibrational analysis confirmed the formation of the R3c phase in all compounds through the characteristic FT-IR absorbance bands assigned to O-Fe-O bending vibration and Fe-O stretching of the octahedral FeO6group in the perovskite, as well as through Raman spectroscopy. The shift of the Raman-active phonon modes in Sm-BFO and Co-BFO NPs indicated structural distortion of the BFO lattice, which resulted in increased local polarization and enhanced visible light absorption. The aqueous dispersion of Co-BFO NPs showed the highest magnetic hyperthermia performance at 30 mT/765 kHz, entering the therapeutic temperature window for cancer treatment, whereas the heating efficiency of all samples was increased with increasing frequency from 375 to 765 kHz, making our doped nanoparticles to be suitable candidates for potential biomedical applications.

Numerical Simulation of Temperature Variations during the Application of Safety Protocols in Magnetic Particle Hyperthermia.

Unavoidably, magnetic particle hyperthermia is limited by the unwanted heating of the neighboring healthy tissues, due to the generation of eddy currents. Eddy currents naturally occur, due to the applied alternating magnetic field, which is used to excite the nanoparticles in the tumor and, therefore, restrict treatment efficiency in clinical application. In this work, we present two simply applicable methods for reducing the heating of healthy tissues by simultaneously keeping the heating of cancer tissue, due to magnetic nanoparticles, at an adequate level. The first method involves moving the induction coil relative to the phantom tissue during the exposure. More specifically, the coil is moving symmetrically-left and right relative to the specimen-in a bidirectional fashion. In this case, the impact of the maximum distance (2-8 cm) between the coil and the phantom is investigated. In the second method, the magnetic field is applied intermittently (in an ON/OFF pulsed mode), instead of the continuous field mode usually employed. The parameters of the intermittent field mode, such as the time intervals (ON time and OFF time) and field amplitude, are optimized based on the numerical assessment of temperature increase in healthy tissue and cancer tissue phantoms. Different ON and OFF times were tested in the range of 25-100 s and 50-200 s, respectively, and under variable field amplitudes (45-70 mT). In all the protocols studied here, the main goal is to generate inside the cancer tissue phantom the maximum temperature increase, possible (preferably within the magnetic hyperthermia window of 4-8 °C), while restricting the temperature increase in the healthy tissue phantom to below 4 °C, signifying eddy current mitigation.

Magnetically driven treatments: optimizing performance by mitigation of eddy currents.

Aim: In this work, we study the eddy current evolution naturally occurring in magnetically driven treatments, such as MRI and magnetic particle hyperthermia (MPH), and propose the mitigation of eddy currents by careful control of field parameters. Materials & methods: We start by simulation of typical MRI and MPH experimental setups to witness eddy currents and then we examine experimentally how field parameters (frequency, amplitude and pulse duration) mitigate eddy currents in a typical MPH treatment. Results and conclusion: By tuning the frequency, the amplitude and by applying pulsed field mode, we successfully attenuate undesirable heating, due to eddy currents' evolution, on surrounding healthy tissues without sparing beneficial effect within the malignant region, thus treatment remains reliable yet with milder side effects.

Toxic and Microbiological Effects of Iron Oxide and Silver Nanoparticles as Additives on Extended Ram Semen.

The aim of the study was to investigate the effect of iron oxide (Fe) and silver (Ag) nanoparticles (NPs) on ram semen. A skim milk extender without antibiotics was used as a diluent of 21 ejaculates (8 rams; 2-3 ejaculates/ram). The groups of control (C; semen without NPs), Fe NPs (3.072 mg Fe3O4/mL semen), and Ag NPs (2.048 mg Ag-Fe/mL semen) were incubated (15 °C; 30 min), and then a magnetic field was used for NPs' removal. Standard microbiological procedures were performed for all groups. Post-treated samples were stored (15 °C) for 24 h, and sperm variables (kinetics by computer assisted sperm analysis (CASA); viability; morphology; HOST; DNA integrity) were evaluated at 6 and 24 h. Semen data were analyzed by a mixed model for repeated measures and microbiological data with Student's t-test for paired samples. At 6 h of storage, VCL and rapid movement-spermatozoa, and at 24 h, total/progressive motility and amplitude of lateral head displacement (ALH) were significantly decreased in group Ag compared to control. In group Fe, progressive/rapid movement-spermatozoa were significantly lower compared to control after 24 h of storage. Only in group Ag was a significant reduction of total bacterial count revealed. In conclusion, the examined Fe NPs demonstrated slight antibacterial effect, while the examined Ag NPs provided higher antibacterial properties accompanied by cytotoxicity.

Mitigation of magnetic particle hyperthermia side effects by magnetic field controls.

Objective: In magnetic particle hyperthermia, a promising least-invasive cancer treatment, malignant regions in proximity with magnetic nanoparticles undergo heat stress, while unavoidably surrounding healthy tissues may also suffer from heat either directly or indirectly by the induced eddy currents, due to the developed electric fields as well. Here, we propose a facile upgrade of a typical magnetic particle hyperthermia protocol, to selectively mitigate eddy currents' heating without compromising the beneficial role of heating in malignant regions.Method: The key idea is to apply the external magnetic field intermittently (in an ON/OFF pulse mode), instead of the continuous field mode typically applied. The parameters of the intermittent field mode, such as time intervals (ON time: 25-100 s, OFF time: 50-200 s, Duty Cycle:16-100%) and field amplitude (30-70 mT) are optimized based on evaluation on healthy tissue and cancer tissue phantoms. The goal is to sustain in cancer tissue phantom the maximum temperature increase (preferably within 4-8°C above body temperature of 37°C), while in the healthy tissue phantom temperature variation is suppressed far below the 4°C dictating the eddy current mitigation.Results: Optimum conditions of intermittent field (ON/OFF: 50/100 in s, Duty Cycle: 33%, magnetic field: 45mT) are then examined in ex-vivo samples verifying the successful suppression of eddy currents. Simultaneously, a well-elaborated theoretical approach provides a rapid calculation of temperature increase and, furthermore, the ability to quickly simulate a variety of duty cycle times and field controls may save experimental time.Conclusion: Eventually, the application of an intermittent field mode in a magnetic particle hyperthermia protocol, succeeds in eddy current mitigation in surrounding tissues and allows for the application of larger field amplitudes that may augment hyperthermia efficiency without objecting typical biomedical applicability field constraints such as Brezovich criterion.

Iron Oxide Nanoparticles as an Alternative to Antibiotics Additive on Extended Boar Semen.

This study examined the effect of Fe3O4 nanoparticles on boar semen. Beltsville thawing solution without antibiotics was used to extend ejaculates from 5 boars (4 ejaculates/boar). Semen samples of control group (C) and group with Fe3O4 (Fe; 0.192 mg/mL semen) were incubated under routine boar semen storage temperature (17 °C) for 0.5 h and nanoparticles were removed by a magnetic field. Before and after treatment, aliquots of all groups were cultured using standard microbiological methods. The samples after treatment were stored (17 °C) for 48 h and sperm parameters (computer-assisted sperm analyzer (CASA) variables; morphology; viability; hypo-osmotic swelling test (HOST); DNA integrity) were evaluated at storage times 0, 24, 48 h. Semen data were analyzed by a repeated measures mixed model and microbial data with Student's t-test for paired samples. Regarding CASA parameters, Fe group did not differ from C at any time point. In group C, total motility after 24 h and progressive motility after 48 h of storage decreased significantly compared to 0 h. In group Fe, linearity (LIN) after 48 h and head abnormalities after 24 h of storage increased significantly compared to 0 h. The microbiological results revealed a significant reduction of the bacterial load in group Fe compared to control at both 24 and 48 h. In conclusion, the use of Fe3O4 nanoparticles during semen processing provided a slight anti-microbiological effect with no adverse effects on sperm characteristics.

The Effect of Polyol Composition on the Structural and Magnetic Properties of Magnetite Nanoparticles for Magnetic Particle Hyperthermia.

A study of the influence of polyols, with or without an additional reducing agent, on crystallites' size and magnetic features in Fe3O4 nanoparticles and on their performance in magnetic particle hyperthermia is presented. Three different samples were synthesized by thermal decomposition of an iron precursor in the presence of NaBH4 in a polyol. So far, triethylene glycol (TrEG) and polyethylene glycol (PEG 1000 and PEG 8000) that exhibit different physical and chemical properties have been used in order to investigate the influence of the polyols on the composition and the size of the NPs. Additionally, the presence of a different reducing agent such as hydrazine, has been tested for comparison reasons in case of TrEG. Three more samples were prepared solvothermally by using the same polyols, which led to different crystallite sizes. The magnetic core of the nanoparticles was characterized, while the presence of the surfactant was studied qualitatively and quantitatively. Concerning the magnetic features, all samples present magnetic hysteresis including remanence and coercivity revealing that they are thermally blocked at room temperature. Finally, a study on the influence of the MNPs heating efficiency from their size and the field amplitude was accomplished. In our polyol process the main idea was to control the specific loss power (SLP) values by the nanoparticles' size and consequently by the polyol itself.

Magnetic hyperthermia efficiency and MRI contrast sensitivity of colloidal soft/hard ferrite nanoclusters.

The use of magnetic nanostructures as theranostic agents is a multiplex task as physiochemical and biochemical properties including excellent magneto-responsive properties, low toxicity, colloidal stability and facile surface engineering capability are all required. Nonetheless, much progress has been made in recent years synthesis of "all-in-one" MNPs remain unambiguously challenging. Towards this direction, in this study is presented a facile incorporation of a soft magnetic phase (MnFe2O4 NPs) with a hard phase (CoFe2O4 NPs) in the presence of the biocompatible polymer sodium dodecyl sulfate (SDS), into spherical and compact bi-magnetic nanoclusters (NCs) with modulated magnetic properties that critically enhance hyperthermic efficiency and MRI contrast effect. Hydrophobic MnFe2O4 and CoFe2O4 NPs coated with oleylamine of the same size (9 nm) were used as primary building units for the formation of the bi-magnetic NCs through a microemulsion approach where a set of experiments were conducted to identify the optimal concentration of SDS (19.5 mM) for the cluster formation. Additionally, homo-magnetic NCs of MnFe2O4 NPs and CoFe2O4 NPs, respectively were synthesized for comparative studies. The presence of distinct magnetic phases within the bi-magnetic NCs resulting in synergistic behavior, where the soft phase offers moderate coercivity Hc and the hard one high magnetization Ms. Increased specific loss power (SLP) value was obtained for the bi-magnetic system (525 W/g) when compared with the homo-magnetic NCs (104 W/g for MnNCs and 223 W/g for CoNCs) under field conditions of 25 kA/m and 765 kHz. Relaxivities (r2) of the bi-magnetic NCs were also higher (81.8 mM-1 s-1) than those of the homo-magnetic NCs (47.4 mM-1 s-1 for MnNCs and 3.1 mM-1 s-1 for CoNCs), while the high r2/r1 value renders the system suitable for T2-weighted MRI imaging.

A novel strategy combining magnetic particle hyperthermia pulses with enhanced performance binary ferrite carriers for effective in vitro manipulation of primary human osteogenic sarcoma cells.

The present study examines the heating efficiency of a combination of manganese or cobalt ferrites in a binary (Co- or Mn-) ferrite nanoparticle form with magnetite, covered with citric acid to improve biocompatibility. The nanoparticle synthesis is based on the aqueous co-precipitation of proper salts, a facile, low-cost, environmentally friendly and high yield synthetic approach. By detailed structural and magnetic characterisation, the direct influence of structural and magnetic features on magnetic hyperthermia concludes to optimum heating efficiency. At a second stage, best performing magnetic nanoparticles undergo in vitro testing in three cell lines: one cancer cell line and two reference healthy cell lines. Both binary ferrite (MnFe2O4/Fe3O4 and CoFe2O4/Fe3O4) appear to be internalised and well tolerated by the cells while a versatile hyperthermia protocol is attempted in an effort to further improve their in vitro performance. Within this protocol, hyperthermia sequences are split in two runs with an intermediate 48 h time interval cell incubation stage while in each run a variable field mode (single or multiple pulses) is applied. Single-pulse field mode represents a typical hyperthermia application scheme where cells undergo the thermal shock continuously. On the other hand multiple-pulses mode refers to multiple, much shorter in duration AC field changes (field ON/OFFs), at each hyperthermia run, resulting eventually in high heating rate and much more harmful cell treatment. Consequently, we propose a novel series of improved performance heat mediators based on ferrite structures which show maximum efficiency at cancer cells when combined with a versatile multiple-pulse hyperthermia module.

Composition and hydrophilicity control of Mn-doped ferrite (MnxFe3-xO4) nanoparticles induced by polyol differentiation.

Manganese doped ferrite (MnxFe3-xO4) nanoparticles with x = 0.29-0.77 were prepared under solvothermal conditions in the presence solely of a polyol using the trivalent manganese and iron acetylacetonates as precursors. In this facile approach, a variety of polyols such as polyethylene glycol (PEG 8000), tetraethylene glycol (TEG), propylene glycol (PG) and a mixture of TEG and PG (1 : 1) were utilized in a triple role as a solvent, a reducing agent and a surface-functionalizing agent. The composition of the fine cubic-spinel structures was found to be related to the reductive ability of each polyol, while determination of structural characteristics plus the inversion parameter (i = 0.18-0.38) were provided by X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy at both the Fe and Mn K-edges. The saturation magnetization increased up to 80 emu g(-1) when x = 0.35 and i = 0.22. In addition, the as-prepared nanocrystals coated with PEG, PG and PG&TEG showed excellent colloidal stability in water, while the TEG-coated particles were not water dispersible and converted to hydrophilic when were extra PEGylated. Measurements of the (1)H NMR relaxation in water were carried out and the nanoprobes were evaluated as potential contrast agents.

In vitro application of Mn-ferrite nanoparticles as novel magnetic hyperthermia agents.

Manganese ferrite nanoparticles were synthesized by a facile, low-cost, environmentally friendly and high yield methodology based on the aqueous co-precipitation of proper salts. Firstly, structural, morphological and magnetic characterization schemes were performed to determine crucial factors for optimizing their heating potential, such as size, polydispersity, saturation magnetization and coercivity. In an effort to simulate the in vivo environment of animal tissue phantoms and study the thermal heating effects resulting from Brownian motion and hysteresis losses, nanoparticles at various concentrations were embedded in aqueous media of varying agar concentration. During the in vitro application healthy cells (primary bone marrow-derived osteoblasts and 3T3-L1 fibroblast-like preadipocytes) and human osteosarcoma Saos-2 cells were incubated with manganese ferrite nanoparticles. The heating profile of the particles was studied at different concentrations and in correlation with their potential cytotoxic effect. Our results revealed concentration dependent cytotoxicity profile and uptake efficiency together with variable specific loss power values yet with fast thermal response, opening novel pathways in material selection as hyperthermia agents.

Novel core-shell magnetic nanoparticles for Taxol encapsulation in biodegradable and biocompatible block copolymers: preparation, characterization and release properties.

Theranostic polymeric nanocarriers loaded with anticancer drug Taxol and superparamagnetic iron oxide nanocrystals have been developed for possible magnetic resonance imaging (MRI) use and cancer therapy. Multifunctional nanocarriers with a core-shell structure have been prepared by coating superparamagnetic Fe3O4 nanoparticles with block copolymer of poly(ethylene glycol)-b-poly(propylene succinate) with variable molecular weights of the hydrophobic block poly(prolylene succinate). The multifunctional polymer nano-vehicles were prepared using a nanoprecipitation method. Scanning transmission electron microscopy revealed the encapsulation of magnetic nanoparticles inside the polymeric matrix. Energy dispersive X-ray spectroscopy and electron energy loss spectroscopy mapping allowed us to determine the presence of the different material ingredients in a quantitative way. The diameter of the nanoparticles is below 250 nm yielding satisfactory encapsulation efficiency. The nanoparticles exhibit a biphasic drug release pattern in vitro over 15 days depending on the molecular weight of the hydrophobic part of the polymer matrix. These new systems where anti-cancer therapeutics like Taxol and iron oxide nanoparticles (IOs) are co-encapsulated into new facile polymeric nanoparticles, could be addressed as potential multifunctional vehicles for simultaneous drug delivery and targeting imaging as well as real time monitoring of therapeutic effects.