优化磁共振纳米医学中磁性纳米粒子的热疗效率

磁共振热疗(magnetic resonance hyperthermia)是近年来新兴的一种纳米医学治疗方法,由磁共振的硬件架构产生特定交变磁场,有效地加热磁性纳米粒子,以直接或间接地杀死癌细胞,体现诊疗一体化。提高磁性纳米粒子的加热效率是当前磁共振热疗领域亟待解决的难题之一。磁性纳米粒子的加热效率不仅与粒子本身的大小、性质以及尺寸分布有关,还和聚集状态有关。该研究利用3D Metropolis蒙特卡罗模拟方法,模拟了不同温度下磁性纳米粒子的磁共振热动力学行为及其团聚与分离现象;并通过修正过的郎之万方程,建立了相变临界温度与外加磁场频率的函数关系。模拟结果显示,磁性纳米粒子悬浮液中多聚体的相对含量随着温度的升高而降低,达到临界温度后,多聚体完全分离成单体;而提高交变磁场频率可以显著降低临界温度,且存在临界频率,高于此临界频率后临界温度不再受外加磁场频率影响,达到稳定。因而在临界频率下预热磁性纳米粒子悬浮液,使得多聚体分离成单体,可优化磁性纳米粒子的热疗效率。     

Study of local magnetic fields and magnetic ordering in fluid and solid matrices containing magnetite nanoparticles using TEMPOL stable radical

The stable nitroxide radical 2,2,6,6-tetramethyl-4-hydroxy-piperidin-1-oxyl (TEMPOL) has been applied as a sensor to study magnetite nanoparticles both in water suspension and in dried gelatin films. g-values and line widths of ESR spectra of the probe were found to be sensitive to the local magnetic fields of magnetic nanoparticles. Calculated on the basis of the sensor ESR spectra, local magnetic fields are stipulated by linear aggregates of magnetite nanoparticles formed in applied outer magnetic fields and are significantly lower than local magnetic fields estimated from the static magnetic measurements data.     

Negative differential viscosity in magnetic suspensions

Recent experiments have shown that the dependence of the macroscopic viscous stress on the mean velocity gradient during the Couette flow of concentrated magnetic suspensions in an external magnetic field is N-shaped. As the field strength is decreased, the amplitude of the N-shaped curve decreases and in the absence of the field, the stress monotonically increases with the shear velocity. A model is proposed to explain the shape of the rheological curve. The model assumes that the magnetic field initiates the formation of dense aggregates in a suspension, which connect the opposite walls of a measurement cell. In the Couette flow, the friction of aggregates on the cell walls causes their deviation from the applied magnetic field through an angle determined by the velocity of the relative motion of the walls. For large enough velocities, the aggregates are detached from the wall and are destroyed by viscous forces. It is shown that the friction of aggregates on cell walls results in the initial increasing and decreasing part of the N-shaped rheogram, while the flow after the detachment of aggregates corresponds to its right increasing part.     

Simulating magnetic nanoparticle behavior in low-field MRI under transverse rotating fields and imposed fluid flow

In the presence of alternating-sinusoidal or rotating magnetic fields, magnetic nanoparticles will act to realign their magnetic moment with the applied magnetic field. The realignment is characterized by the nanoparticle's time constant, τ. As the magnetic field frequency is increased, the nanoparticle's magnetic moment lags the applied magnetic field at a constant angle for a given frequency, Ω, in rad s⁻¹. Associated with this misalignment is a power dissipation that increases the bulk magnetic fluid's temperature which has been utilized as a method of magnetic nanoparticle hyperthermia, particularly suited for cancer in low-perfusion tissue (e.g., breast) where temperature increases of between 4 and 7 °C above the ambient in vivo temperature cause tumor hyperthermia. This work examines the rise in the magnetic fluid's temperature in the MRI environment which is characterized by a large DC field, B₀. Theoretical analysis and simulation is used to predict the effect of both alternating-sinusoidal and rotating magnetic fields transverse to B₀. Results are presented for the expected temperature increase in small tumors ( radius) over an appropriate range of magnetic fluid concentrations (0.002-0.01 solid volume fraction) and nanoparticle radii (1-10 nm). The results indicate that significant heating can take place, even in low-field MRI systems where magnetic fluid saturation is not significant, with careful the goal of this work is to examine, by means of analysis and simulation, the concept of interactive fluid magnetization using the dynamic behavior of superparamagnetic iron oxide nanoparticle suspensions in the MRI environment. In addition to the usual magnetic fields associated with MRI, a rotating magnetic field is applied transverse to the main B₀ field of the MRI. Additional or modified magnetic fields have been previously proposed for hyperthermia and targeted drug delivery within MRI. Analytical predictions and numerical simulations of the transverse rotating magnetic field in the presence of B₀ are investigated to demonstrate the effect of Ω, the rotating field frequency, and the magnetic field amplitude on the fluid suspension magnetization. The transverse magnetization due to the rotating transverse field shows strong dependence on the characteristic time constant of the fluid suspension, τ. The analysis shows that as the rotating field frequency increases so that Ωτ approaches unity, the transverse fluid magnetization vector is significantly non-aligned with the applied rotating field and the magnetization's magnitude is a strong function of the field frequency. In this frequency range, the fluid's transverse magnetization is controlled by the applied field which is determined by the operator. The phenomenon, which is due to the physical rotation of the magnetic nanoparticles in the suspension, is demonstrated analytically when the nanoparticles are present in high concentrations (1-3% solid volume fractions) more typical of hyperthermia rather than in clinical imaging applications, and in low MRI field strengths (such as open MRI systems), where the magnetic nanoparticles are not magnetically saturated. The effect of imposed Poiseuille flow in a planar channel geometry and changing nanoparticle concentration is examined. The work represents the first known attempt to analyze the dynamic behavior of magnetic nanoparticles in the MRI environment including the effects of the magnetic nanoparticle spin-velocity. It is shown that the magnitude of the transverse magnetization is a strong function of the rotating transverse field frequency. Interactive fluid magnetization effects are predicted due to non-uniform fluid magnetization in planar Poiseuille flow with high nanoparticle concentrations.     

Synthesis,characterization and a.c. magnetic analysis of magnetite nanoparticles

In the last years, the study of Fe-based magnetic nanoparticles (MNP) has attracted increasing interest either for the physical properties shown by nanosized materials (electric and magnetic properties are strongly affected by dimension and surface effects) either for the different technological applications of these materials (catalysis, drug delivery, magnetic resonance imaging, contaminants removal from groundwater, new exchange coupled magnets, soft nanomagnets for high frequency applications, etc.). In this article, the results obtained in the synthesis and characterization of the Fe₃O₄ MNP is reported. The magnetite nanoparticles were synthesized by a modified Massart method. Structural characterization was performed using X-ray diffraction analysis and a complete morphological and dimensional study was carried out by means of Transmission Electron Microscopy, and a.c. magnetic susceptibility measured as a function of the frequency of the applied magnetic field. Diameters of the superparamagnetic Fe₃O₄ nanoparticles are ranging from 2 to 10 nm, as evidenced by all the techniques employed. The size distribution of the hydrated aggregates in solution has been obtained by quantitative analysis of the frequency dependence of the a.c. susceptibility. The mathematical approach adopted will be described and all the obtained results will be compared and discussed.     

Forced diffusion in magnetic fluids under the influence of a strong magnetic field gradient

We have investigated the forced diffusion of magnetic nanoparticles suspended in a carrier liquid under the influence of a magnetic field gradient. A cylindrical layer of the suspension was exposed to an azimuthal magnetic field with radial gradient. The radial distribution of the concentration of magnetic particles was determined for different times. The obtained experimental data are compared with a numerical solution of the diffusion equation and good agreement has been observed.     

Interaction of a droplet magnetic fluid with a variable magnetic field

The subject of investigation is the effective magnetic susceptibility of a droplet magnetic fluid. It is found that the rotation of such a medium causes the intriguing behavior of its magnetization due to the probing-field-induced deformation of droplet aggregates followed by their reorientation under rotation. To confirm this, the deformation of droplet aggregates subjected to a variable magnetic field is studied. In the case of the variable magnetic field, the threshold strength causing deformation is much lower than in the case of the constant field and depends on the field frequency.     

Synthesis and investigation of precipitated ensembles of magnetic nanoparticles with controlled easy axis orientation

Two samples with immobilized magnetic nanoparticles are synthesized and investigated. The first sample has randomly oriented easy axes of magnetic anisotropy; the second sample has preferentially aligned easy axes, produced via the precipitation of a colloid of ferromagnetic particles in the presence of a magnetic field. It is shown that the precipitation of an aqueous suspension of nanoparticles in the presence of a magnetic field greatly changes the anisotropy of a sample, compared to one prepared by precipitation without a magnetic field. The second sample exhibits a preferential direction of the easy axes of magnetic anisotropy that coincides with the direction of the external magnetic field applied in the drying process of sample preparation.     

Effect of the number of iron oxide nanoparticle layers on the magnetic properties of nanocomposite LbL assemblies

Aqueous colloidal suspension of iron oxide nanoparticles has been synthesized. Z-potential of iron oxide nanoparticles stabilized by citric acid was −35±3 mV. Iron oxide nanoparticles have been characterized by the light scattering method and transmission electron microscopy. The polyelectrolyte/iron oxide nanoparticle thin films with different numbers of iron oxide nanoparticle layers have been prepared on the surface of silicon substrates via the layer-by-layer assembly technique. The physical properties and chemical composition of nanocomposite thin films have been studied by atomic force microscopy, magnetic force microscopy, magnetization measurements, Raman spectroscopy. Using the analysis of experimental data it was established, that the magnetic properties of nanocomposite films depended on the number of iron oxide nanoparticle layers, the size of iron oxide nanoparticle aggregates, the distance between aggregates, and the chemical composition of iron oxide nanoparticles embedded into the nanocomposite films. The magnetic permeability of nanocomposite coatings has been calculated. The magnetic permeability values depend on the number of iron oxide nanoparticle layers in nanocomposite film.     

Quasi-2D Monte Carlo simulations of the regime change in the aggregates of magnetic cubic particles on a material surface

We have investigated the aggregate structure of a suspension composed of magnetic particles with a cubic geometry by means of Monte Carlo simulations. From the viewpoint of application to the technology of surface modification, we have considered a quasi-two-dimensional suspension in thermodynamic equilibrium. As the magnetic interaction strength is increased, the effects of the thermal energy are reduced and the particles tend to aggregate together. These aggregates of cubic particles are not chain-like, but are designated as closely packed clusters. An applied magnetic field tends to enhance the formation of clusters along the field direction but does not significantly regularise the internal structure of the cluster. This is mainly due to the preference of a face-to-face contact configuration for the alignment of particles with cubic geometry. The regime of the internal structure of aggregates has a significant effect on the characteristics of the alignment of the magnetic moments with regard to the external magnetic field direction. Our simulations indicate that larger closely packed clusters are formed with increasing volumetric fraction, whereas the internal structure of the closely packed clusters is not found to be significantly influenced by the change in the volumetric fraction.     

Ultrasonic investigation of magnetic nanoparticles suspension with PEG biocompatible coating

Water suspension of nanoparticles was studied by ultrasound spectroscopy. Nanoparticles have a core-shell structure with magnetic core Fe₃O₄ and surfactant shells. The surface of magnetic particles was coated with oleate sodium as the primary layer and polyethylene glycol as the secondary layer. The acoustic properties of suspensions, such as velocity and attenuation of ultrasonic waves, have been measured. From experimental data mechanical properties have been determined. Adiabatic compressibility of nanoparticles suspension decreased with increase of temperature. The changes of ultrasonic wave attenuation under the influence of the external magnetic field, show that magnetic liquids with high concentration of magnetic material (despite two surfactant shells) show tendency to aggregate.     

Analysis of the ferromagnetic resonance spectra of aggregates of magnetite nanoparticles formed by a magnetic field

The ferromagnetic resonance (FMR) spectra of magnetite nanoparticles in aqueous solutions and solid polymer films were analyzed at different particle concentrations, matrix rigidities, temperatures, external magnetic effects, and positions of flat samples in the field of the spectrometer. The formation of linear aggregates of nanoparticles under the influence of magnetic fields is the major factor that changes the FMR spectrum shape and position. The results were analyzed in terms of phenomenological theory of FMR. The applicability of the equations of phenomenological theory was verified, and the fraction of nanoparticles in linear aggregates was evaluated.     

Polarization and transmission of microwaves in the magnetic suspension in the applied magnetic field

The production method of magnetic suspension consisting of ferromagnetic particles dispersed in cedarwood oil is presented at the beginning of this article. Next, the set-up for microwaves generation using a klystron is described. The main part of this paper concerning microwave transmission and polarization during its passage in samples of the produced magnetic suspension placed in a magnetic field is based on the following parameters: induction of this field, filling factor of magnetic suspension by ferromagnetic particles, dimensions of particles, viscosity of liquid carrier, and ratio of the magnetic field changes. Conducted investigations show that microwaves are damped and polarized in these magnetic suspensions. Obtained results are discussed and observed effects are explained by ordering of ferromagnetic particles in magnetic suspension by applied magnetic field.     

Radial breathing-mode frequency of elastically confined spherical nanoparticles subjected to circumferential magnetic field

Knowledge of the vibrational properties of nanoparticles is of fundamental interest since it is a signature of their morphology, and it can be utilized to characterize their physical properties. In addition, the vibration characteristics of the nanoparticles coupled with surrounding media and subjected to magnetic field are of recent interest. This paper develops an analytical approach to study the radial breathing-mode frequency of elastically confined spherical nanoparticles subjected to magnetic field. Based on Maxwell's equations, the nonlocal differential equation of radial motion is derived in terms of radial displacement and Lorentz's force. Bessel functions are used to obtain a frequency equation. The model is justified by a good agreement between the results given by the present model and available experimental and atomic simulation data. Furthermore, the model is used to elucidate the effect of nanoparticle size, the magnetic field and the stiffness of the elastic medium on the radial breathing-mode frequencies of several nanoparticles. Our results reveal that the effects of the magnetic field and the elastic medium are significant for nanoparticle with small size.     

Nonlinear oscillation characteristics of magnetic microbubbles under acoustic and magnetic fields

Microbubbles loaded with magnetic nanoparticles (MMBs) have attracted increasing interests in multimode imaging and drug/gene delivery and targeted therapy. However, the dynamic behaviors generated in diagnostic and therapeutic applications are not clear. In the present work, a novel theoretical model of a single MMB was developed, and the dynamic responses in an infinite viscous fluid were investigated under simultaneous exposure to magnetic and acoustic fields. The results showed that the amplitude reduces and the resonant frequency increases with the strength of the applied steady magnetic field and the susceptibility of the magnetic shell. However, the magnetic field has a limited influence on the oscillating. It is also noticed that the responses of MMB to a time-varying magnetic field is different from a steady magnetic field. The subharmonic components increase firstly and then decrease with the frequency of the magnetic field and the enhanced effect is related to the acoustic driving frequency. It is indicated that there may be a coupling interaction effect between the acoustic and magnetic fields.     

A simple method to estimate the magnetic moment of magnetic micro-particles

Micro-particles in suspension in a fluid are an example of a very low Reynolds number problem. In this case, no inertial effects are observed. Magnetic micro-particles with magnetic moment m, suspended in a fluid orient to applied external magnetic fields B due to the interaction between the field and the magnetic moment. In this work, we present a simple method to estimate the total magnetic moment of magnetic micro-organisms. The method is based on the application of an external oscillating magnetic field in the sites where the micro-organisms are. In this case, it is possible to obtain theoretically the solution of the equation of motion (rotation of the organism and its trajectory). The solution is a transcendental equation relating the orientation angle and m and can be solved by numerical methods. Changing the frequency and/or the field intensity, it is possible to obtain a situation in which the crystal rotates uninterruptedly (a resonance regime). This condition is related to the applied field intensity, to the frequency, to the medium viscosity, to the crystal dimension, and to the micro-crystal magnetic moment m. The method can be used to estimate the total cellular magnetic moment of magnetic micro-particles.     

The influence of long range interparticle correlations on the magnetically induced optical anisotropy in magnetic colloids

In this paper we develop a theoretical model for the magnetically induced optical anisotropy in dense magnetic colloids made of spherical and un-aggregated magnetic monodomain nanoparticles. Both dipole-field and dipole-dipole magnetic and electric interactions between the magnetic monodomain particles are taken into account in the Hamiltonian of the system. Using the pair correlation function in a colloidal suspension of magnetic nanoparticles developed by Ivanov and Kuznetsova (2001) [11], the complex dielectric constant of a magnetic colloid is modeled as a function of the light polarization direction, the magnetic field intensity and magnetic particle concentration and diameter. The two main features of the model are that, on the one hand, it predicts the possibility of magnetically induced optical anisotropy in dense magnetic colloids made of spherical and un-aggregated monodomain nanoparticles, and on the other hand, unlike the existing models for diluted samples, it predicts a non-linear dependence of dichroism and birefringence on magnetic particle concentration.     

Quasi-2D Monte Carlo simulations of phase transitions and internal aggregate structures in a highly dense suspension composed of magnetic plate-like particles

The phase transitions and the internal aggregate structures of a highly dense suspension composed of magnetic plate-like particles with a magnetic moment normal to the particle axis have been investigated by means of the Monte Carlo method. The present study considered a quasi-2D system in order to clarify the influences of the volumetric fraction of particles and the magnetic field strength on particle aggregations and phase transitions. The internal structures of particle aggregates have been discussed quantitatively in terms of pair correlation functions, orientational pair correlation functions, nematic and polar order parameters. The main results obtained here are summarized as follows. When the influence of the magnetic interaction between particles is of the same order of that of the perpendicular magnetic field strength, the particles form column-like clusters, and the internal structure of the suspension shows solid-like structures. For the case of a strong applied magnetic field, the internal structure is transformed from solid-like structures into isotropic ones. However, as the volumetric fraction increases, the particles form brick wall-like structures under the situation of a strong applied magnetic field, and the internal structure exhibits solid-like ones. The brick wall-like structures also appear for a relatively weak magnetic field applied along the in-plane direction despite a slightly smaller volumetric fraction compared with the case of the perpendicular applied magnetic field.     

New aspects of energy transfer from an alternating magnetic field to a pendulum with ferromagnetic suspension

New data are presented about energy transfer from an alternating magnetic field to a pendulum with ferromagnetic suspension. For each frequency of the alternating magnetic field there is a certain field intensity for which energy transfer is maximum.     

Thermosensitive magnetic polymer particles as contactless controllable drug carriers

Spherically shaped thermosensitive micro and nanoparticles based on N-isopropylacrylamide were synthesized using a novel inverse suspension polymerization technique which enables a bead formation within minutes. In addition to the rapidity, the suspension procedure provides an effective platform for the encapsulation of magnetic colloids and simultaneous drug analogous substances. The presence of the magnetic colloids allows an inductive heating of the particles using an alternating magnetic field above the polymer transition temperature (>35 °C). This results in a pronounced de-swelling accompanied by a release of the encapsulated substances. The potential of this technology for a new contactless controllable drug releasing approach is exemplarily demonstrated using rhodamine B and methylene blue as drug analogous substances.