Magnetic Nanoparticles For Hyperthermia Applications Research Articles

Design and Modelling of an Induction Heating Coil to Investigate the Thermal Response of Magnetic Nanoparticles for Hyperthermia Applications

Magnetic Field Hyperthermia is a technique where tumours are treated through an increase in local temperature upon exposure to alternating magnetic fields (AMFs) that are mediated by magnetic nano-particles (MNPs). In an AMF, these particles heat-up and kill the cells. The relationship between an AMF and the heating-rate is complex, leading to confusion when comparing data for different MNP and AMF conditions. This work allows for the thermal-response to be monitored at multiple AMF amplitudes while keeping other parameters constant. An induction-heating coil was designed based on a Zero-Voltage-Zero-Current (ZVZC) resonant circuit. The coil operates at 93 kHz with a variable DC drive-voltage (12–30 V). NEC4 software was used to model the magnetic field distribution, and MNPs were synthesised by the coprecipitation method. The magnetic field was found to be uniform at the centre of the coil and ranged from 1 kAm−1 to 12 kAm−1, depending on the DC drive-voltage. The MNPs were found to have a specific absorption rate (SAR) of 1.37 Wg−1[Fe] and 6.13 Wg−1[Fe] at 93 kHz and 2.1 kAm−1 and 12.6 kAm−1, respectively. The measured SAR value was found to be directly proportional to the product of the frequency and field-strength (SARα f Ho). This leads to the recommendation that, when comparing data from various groups, the SAR value should be normalized following this relationship and not using the more common relationship based on the square of the field intensity (SARα f Ho2).

Effect of Gd substitution on structure, optical and magnetic properties, and heating efficiency of Fe3O4 nanoparticles for magnetic hyperthermia applications

This work presents the synthesis of Fe3-xGdxO4 nanoparticles and the investigation of the impact of Gd content (x) on structural characteristics of nanoparticles, including lattice parameters, crystallite size, and X-ray density. The high-resolution images of Transmission Electron Microscopy reveal that the synthesized Fe3-xGdxO4 nanoparticles have a narrow distribution in size statistics between 9 and 12.5 nm. Interestingly, analyzing different prepared samples reveals that both the saturation magnetization and magnetic anisotropy decrease simultaneously with the increase of band gap while remaining independent of the specific absorption rate (SAR) value. The SAR is greater than that of pure Fe3O4 nanoparticles. In a specific case of Fe2.75Gd0.25O4 sample where the optimal value of x is 0.25, the highest SAR value obtained is 237.4 W/g. Besides, the experimental results demonstrate an optimal doping content with the highest SAR value of Fe2.75Gd0.25O4 nanoparticles along with the theoretical explanation by analyzing the Linear Theory Response framework based on the relationship between magnetic anisotropy and diameter with SAR value. The theoretical and experimental evidence fully demonstrate that doping is an effective approach for optimizing as-synthesized NPs to enable efficient hyperthermia applications.

Specific loss power of magnetic nanoparticles: A machine learning approach

A machine learning approach has been applied to the prediction of magnetic hysteresis properties (coercive field, magnetic remanence, and hysteresis loop area) of magnetic nanoparticles for hyperthermia applications. Trained on a dataset compiled from numerical simulations, a neural network and a random forest were used to predict power losses of nanoparticles as a function of their intrinsic properties (saturation, anisotropy, and size) and mutual magnetic interactions, as well as of application conditions (temperature, frequency, and applied field magnitude), for values of the parameters not represented in the database. The predictive ability of the studied machine learning approaches can provide a valuable tool toward the application of magnetic hyperthermia as a precision medicine therapy tailored to the patient’s needs.

Effect of the distribution of anisotropy constants on the magnetic properties of iron oxide nanoparticles

The distribution of shape anisotropy constants in two colloids of iron oxide nanoparticles has been measured from the distribution of particle elongations within each system. The results are in good agreement with the values calculated from a temperature decay of remanence measurement. For a fluid with a saturation magnetisation of 420 emu/cc and an average particle elongation of ∼ 1.3, the distribution of energy barriers is controlled by both the distribution of particle sizes and particle elongations. For a fluid with a saturation magnetisation of 320 emu/cc and a wide distribution of particle sizes, the energy barrier to reversal can be assumed to be controlled by the distribution of particle volumes. These results highlight the need to take into account the distribution of anisotropy constants when making predictions of the heating properties of assemblies of magnetic nanoparticles for hyperthermia applications.

Maghemite (γ-Fe2O3) and γ-Fe2O3-TiO2 Nanoparticles for Magnetic Hyperthermia Applications: Synthesis, Characterization and Heating Efficiency.

In this report, the heating efficiencies of γ-Fe2O3 and hybrid γ-Fe2O3-TiO2 nanoparticles NPs under an alternating magnetic field (AMF) have been investigated to evaluate their feasible use in magnetic hyperthermia. The NPs were synthesized by a modified sol-gel method and characterized by different techniques. X-ray diffraction (XRD), Mössbauer spectroscopy and electron microscopy analyses confirmed the maghemite (γ-Fe2O3) phase, crystallinity, good uniformity and 10 nm core sizes of the as-synthesized composites. SQUID hysteresis loops showed a non-negligible coercive field and remanence suggesting the ferromagnetic behavior of the particles. Heating efficiency measurements showed that both samples display high heating potentials and reached magnetic hyperthermia (42 °C) in relatively short times with shorter time (~3 min) observed for γ-Fe2O3 compared to γ-Fe2O3-TiO2. The specific absorption rate (SAR) values calculated for γ-Fe2O3 (up to 90 W/g) are higher than that for γ-Fe2O3-TiO2 (~40 W/g), confirming better heating efficiency for γ-Fe2O3 NPs. The intrinsic loss power (ILP) values of 1.57 nHm2/kg and 0.64 nHm2/kg obtained for both nanocomposites are in the range reported for commercial ferrofluids (0.2–3.1 nHm2/kg). Finally, the heating mechanism responsible for NP heat dissipation is explained concluding that both Neel and Brownian relaxations are contributing to heat production. Overall, the obtained high heating efficiencies suggest that the fabricated nanocomposites hold a great potential to be utilized in a wide spectrum of applications, particularly in magnetic photothermal hyperthermia treatments.

Synthesis and Characterization of Oleic Acid Coated Magnetic Nanoparticles for Hyperthermia Applications

In this study, we aimed to synthesize stable dispersions of iron oxide nanoparticles (IONs) coated with different amounts of oleic acid (OA) suitable for magnetic nano hyperthermia applications. For this purpose, bare and different amounts of oleic acid (0.2%, 0.5% and 1.0%, v/v) coated IONs were prepared by co-precipitation method. Then, their structures, morphologies, magnetic properties and heating abilities were characterized by using suitable techniques. IONs+1.0%OA nanoparticles showed low agglomeration with high dispersion capacity. Moreover, 1.0% OA coating showed the highest heating ability with a temperature increase of (25.2 °C) compared to IONs+OA (0.2%, 16.4 °C; 0.5%, 19 °C), but similar with bare IONs (26.7 °C). The specific absorption rate (SAR) values of bare IONs and IONs+OA (0.2%, 0.5%, 1.0% v/v) were found as 39.50, 34.81, 23.36 and 45.98 W/g, respectively. Our results showed that the comparable hyperthermia effect of IONs+1.0%OA with bare IONs was attributable to their uniform dispersion performance along with higher SAR values. We concluded that the dispersion of hydrophobic IONs+OA in an aqueous medium is one of the critical requirements for increasing temperature in magnetic nano hyperthermia applications.

Citric acid coated CoFe2O4 nanoparticles transformed through rapid mechanochemical ligand exchange for efficient magnetic hyperthermia applications

Abstract We report the hydrothermal synthesis of uniform size (∼6 nm) oleic acid capped CoFe 2 O 4 (OA-CoFe 2 O 4 ) nanoparticles. These OA-CoFe 2 O 4 nanoparticles were initially hydrophobic and not dispersible in water which were transformed into hydrophilic nanoparticles by modifying their surface with citric acid using a rapid mechanochemical ligand exchange process, which makes CoFe 2 O 4 nanoparticles stable colloidal solution in water. The synthesized citric acid coated CoFe 2 O 4 (CA-CoFe 2 O 4 ) nanoparticles show a high enough and stable zeta potential over 120 days. CA-CoFe 2 O 4 nanoparticles exhibited high biocompatibility under in vitro cell studies. The specific absorption rate (SAR) of the CA-CoFe 2 O 4 nanoparticles was measured by induction heating studies. Upon the exposure of AC external magnetic field, the viability of cancer cells was reduced considerably, suggesting efficient potentiality of these CA-CoFe 2 O 4 nanoparticles for Magnetic Hyperthermia Applications. Present mechanochemical ligand exchange method is proposed as an efficient method for large scale production of biocompatible and water dispersible magnetic oxide nanoparticles for Magnetic Hyperthermia Applications.

Measurement of the distribution of anisotropy constants in magnetic nanoparticles for hyperthermia applications

In this work, we have applied theoretical calculations to new experimental measurements of the effect of the anisotropy distribution in magnetite nanoparticles, which in turn controls hysteresis heating for hyperthermia applications. Good agreement between theory and experiment is reported where the theoretical calculation is based upon the detailed measurement of the particle elongation generally observed in the nanoparticles. The elongation has been measured from studies via transmission electron microscopy. We find that particle elongation is responsible for the anisotropy dispersion, which can be obtained by analysis and fitting to a measurement of the temperature decay of remanence. A median value of the anisotropy constant of 1.5 × 105 erg/cc was obtained. A very wide distribution of anisotropy constants is present with a Gaussian standard deviation of 1.5 × 105 erg/cc. From our measurements, deviations in the value of the saturation magnetisation from particle to particle are most likely the main factor giving rise to this large distribution, with 33% arising from the error in the measured elongation. The lower limit to the anisotropy constant of the nanoparticles is determined by the magnetocrystalline anisotropy of the material, 1.1 × 105 erg/cc for magnetite, which was studied in this work.

Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications.

Magnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR). The SAR of Fe3O4 nanoparticles with two different mean sizes, and Ni1-xZnxFe2O4 ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69kHz and ≈ 100kHz respectively) and rf magnetic field peak values (up to 100mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents. Dynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples. A means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods. This work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

Mössbauer investigations of Fe and Fe3O4 magnetic nanoparticles for hyperthermia applications

Magnetic nanoparticles of magnetite Fe3O4 and Fe synthesized by physical vapor deposition with a fast highly effective method using a solar energy have been studied. Targets have been prepared from tablets pressed from Fe3O4 or Fe powders. Relationships between the structure of nanoparticles and their magnetic properties have been investigated in order to understand principles of the control of the parameters of magnetic nanoparticles. Mossbauer investigations have revealed that the nanoparticles synthesized from tablets of both pure iron and Fe3O4 consist of two phases: pure iron and iron oxides (γ-Fe2O3 and Fe3O4). The high iron oxidability suggests that the synthesized nanoparticles have a core/shell structure, where the core is pure iron and the shell is an oxidized iron layer. Magnetite nanoparticles synthesized at a pressure of 80 Torr have the best parameters for hyperthermia due to their core/shell structure and core-to-shell volume ratio.

An air-cooled Litz wire coil for measuring the high frequency hysteresis loops of magnetic samples--a useful setup for magnetic hyperthermia applications.

A setup for measuring the high-frequency hysteresis loops of magnetic samples is described. An alternating magnetic field in the range 6-100 kHz with amplitude up to 80 mT is produced by a Litz wire coil. The latter is air-cooled using a forced-air approach so no water flow is required to run the setup. High-frequency hysteresis loops are measured using a system of pick-up coils and numerical integration of signals. Reproducible measurements are obtained in the frequency range of 6-56 kHz. Measurement examples on ferrite cylinders and on iron oxide nanoparticle ferrofluids are shown. Comparison with other measurement methods of the hysteresis loop area (complex susceptibility, quasi-static hysteresis loops, and calorific measurements) is provided and shows the coherency of the results obtained with this setup. This setup is well adapted to the magnetic characterization of colloidal solutions of magnetic nanoparticles for magnetic hyperthermia applications.

Bacterially synthesized ferrite nanoparticles for magnetic hyperthermia applications.

Magnetic hyperthermia uses AC stimulation of magnetic nanoparticles to generate heat for cancer cell destruction. Whilst nanoparticles produced inside magnetotactic bacteria have shown amongst the highest reported heating to date, these particles are magnetically blocked so that strong heating occurs only for mobile particles, unless magnetic field parameters are far outside clinical limits. Here, nanoparticles extracellularly produced by the bacteria Geobacter sulfurreducens are investigated that contain Co or Zn dopants to tune the magnetic anisotropy, saturation magnetization and nanoparticle sizes, enabling heating within clinical field constraints. The heating mechanisms specific to either Co or Zn doping are determined from frequency dependent specific absorption rate (SAR) measurements and innovative AC susceptometry simulations that use a realistic model concerning clusters of polydisperse nanoparticles in suspension. Whilst both particle types undergo magnetization relaxation and show heating effects in water under low AC frequency and field, only Zn doped particles maintain relaxation combined with hysteresis losses even when immobilized. This magnetic heating process could prove important in the biological environment where nanoparticle mobility may not be possible. Obtained SARs are discussed regarding clinical conditions which, together with their enhanced MRI contrast, indicate that biogenic Zn doped particles are promising for combined diagnostics and cancer therapy.

Synthesis and functionalisation of magnetic nanoparticles for hyperthermia applications

A summary of recent developments in the synthesis, stabilisation and coating of magnetic iron oxide nanoparticles for hyperthermia applications is presented. Methods for synthesis in aqueous, organic and microemulsion systems are reviewed together with the resulting heating rates of the nanoparticles. Different stabilisation mechanisms for iron oxide nanoparticles from aqueous and organic media are discussed as intermediates for further coating and functionalisation. Coating with silica and/or polysaccharides is mainly used for design of nanoparticles especially for targeted hyperthermia application. These coatings permit versatile functionalisation as a basis for conjugating biomolecules, e.g. antibodies or peptides. Various strategies to conjugate biomolecules on the particle surface are discussed, with emphasis on methods that preserve biofunctionality after immobilisation. The efficiency of established methods such as carbodiimide coupling and oriented conjugation strategies is compared with new developments such as the bioorthogonal approaches that are based on the cycloaddition of strain-promoted alkynes with azides or nitrones. For targeted hyperthermia applications the study of the formation of a protein corona around nanoparticles with site-specific biomolecules on the surface is essential to achieve improved circulation times in the blood and reduced non-specific uptake by non-targeted organs for a high specific accumulation in the target tissue.

Effect of the distribution of anisotropy constants on hysteresis losses for magnetic hyperthermia applications

Magnetic hyperthermia using magnetic nanoparticles is a potential remedial therapy for the reduction of cancer and other tumours. The dominant heating mechanism is hysteresis heating. This means that control of the particle size distribution is essential. However, control of the anisotropy dispersion is also required. We have calculated the effect of the anisotropy distribution on the hysteresis heating in magnetic nanoparticles for hyperthermia applications. Where there is a wide distribution of anisotropy constants the heat output is controlled by the distribution of anisotropy constants. This effect is significant in systems such as magnetite particles where shape anisotropy dominates.

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.

Synthesis and characterization of polymer encapsulated Cu–Ni magnetic nanoparticles for hyperthermia applications

Copper nickel alloy nanoparticles were synthesized by polyol reduction method and by physical melting process. The particles were further coated with a biodegradable polymer, polyethylene glycol. The particles have a curie temperature in the range of 43–46 °C and are designed to be used for hyperthermia applications. Morphology of these encapsulated particles was determined by electron microscopy. The curie temperature for alloy particles and encapsulated particles was also measured.