优化磁共振纳米医学中磁性纳米粒子的热疗效率（英文）

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.     

纳米磁性药物靶向动力学模拟

基于Navier-Stokes方程与Maxwell-Ampere理论建立了肿瘤细动脉中血液的非定常脉动模型,在磁场和流场耦合状态下研究引入纳米磁性药物后磁场对血液流场的影响.把离散模型和单相模型耦合,用有限元方法对纳米磁性药物在细动脉中的传输进行动力学模拟.模拟结果表明,磁场对纳米尺度磁性粒子的俘获形式明显不同于对微米尺度粒子,纳米磁性粒子运动轨迹与血液流线基本重合.由于磁性纳米粒子的存在,磁场影响了血液的流场分布,在磁体附近形成涡流区并长期滞留,以此方式实现对磁性药物的俘获.     

生物体中的生物磁性纳米粒子及基因调控机制

生物磁性纳米粒子在所有三个生命领域的有机体中存在着,包括在原核生物、古细菌和真核生物中.这些生物体中的生物磁性纳米粒子具有相似的物理化学特性,也随着物种的不同存在着差别.在人体中的正常组织和病变组织中同样存在着生物磁性纳米粒子,这些粒子与其它物种中的生物磁性纳米粒子具有相似性和区别,人体病变组织中生物磁性纳米粒子数量的增多与人类神经退行性病变、癌症和动脉粥样硬化病等疾病有着密切的关系.基于比较基因组学研究方法,科学家认为生物体中生物磁性纳米粒子生物矿化过程有相似的基因调控机制,并给出了预测的基因调控机制模型.本文对以上内容做了简要描述,希望对有关研究提供借鉴.     

Fe3O4纳米粒子对P3HT:PCBM电池的影响

为了提高太阳能电池的性能,研究磁性纳米粒子在外加磁场的作用下对聚合物太阳能电池有源层P3HT:PCBM成膜及太阳能电池性能的影响。本文采用热分解法制备了磁性Fe₃O₄纳米粒子,将不同质量分数的Fe₃O₄纳米粒子掺入到P3HT:PCBM溶液中,旋涂后在外加磁场的作用下自组成膜。通过TEM、XRD对制备的Fe₃O₄纳米粒子进行表征,并利用偏光显微镜、原子力显微镜对成膜质量进行探究。结果表明,采用热分解法制备的Fe₃O₄纳米粒子直径在10 nm左右,在外加磁场作用下,Fe₃O₄纳米粒子对成膜有一定的调控作用。当Fe₃O₄纳米粒子掺杂质量分数为1%时,太阳能电池器件的开路电压增加3.77%,短路电流增加24.93%,光电转换效率提高7.82%。     

磁性核壳纳米粒子的制备及其在分离和光谱检测中的应用

磁性及其核壳复合纳米粒子由于在不同领域中具有广泛应用而受到研究者的极大关注,总结了磁性及磁性核壳纳米粒子常见的制备方法及各自的特点,并重点讨论了其在磁分离及光谱检测方面的应用,也介绍了本课题组在纳米粒子合成及应用方面所做的一部分工作。最后对磁性纳米粒子中存在的问题进行了探讨,并对其应用前景进行了展望。     

铂纳米粒子热稳定性的原子级模拟研究

本文采用分子动力学结合嵌入原子多体势,模拟了铂纳米粒子在升温过程中的热稳定性和熔化机制,并利用共近邻分析方法分析了它的微结构演化过程。模拟的结果表明：铂纳米粒子的熔点明显低于体材料的熔点;由于表面层原子的结合力较弱,在升温过程中表面会首先出现预熔;纳米粒子的熔化是从表面层开始的,并随着温度的升高,熔化的表面层会逐渐向内部扩展,最终导致纳米粒子整体转变为液态结构;当温度低于表面预熔温度时,纳米粒子保持良好的晶态结构。     

Fe3O4@SiO2@An磁性纳米荧光粒子的制备及对锌离子的识别

通过微乳法一步合成了SiO2包覆Fe3O4的磁性纳米颗粒(MNP)并通过硅烷偶联剂将表面氨基化,进一步通过化学成键将荧光分子蒽修饰到氨基化的纳米粒子表面,制得Fe3O4@SiO2@An磁性纳米荧光粒子.采用XRD、TEM、FTIR等实验方法对该粒子进行一系列的表征,其直径约为9nm,常温时具有超顺磁性,通过外加磁场,能够使粒子从溶液中简单有效地分离.该粒子在溶剂中具有较好的分散性,荧光实验表明,对锌离子具有较好的选择性,在锌离子存在下基于光诱导电子转移( PET,PhotoinducedElectron Transfer)机理,粒子荧光强度显著增强,检出限为2.8571×10-5mol/L.     

磁性液体中非磁性小球与磁性纳米颗粒的相互作用及磁组装

利用磁性液体与聚苯乙烯小球溶液混合得到的复合磁性液体, 研究了聚苯乙烯小球和磁性纳米颗粒在外加磁场作用下的动力学过程. 实验结果表明, 当外加磁场的方向平行于样品平面时, 聚苯乙烯小球在沿着磁场的方向上表现出相互吸引而形成链状结构, 其动力学过程可分为聚苯乙烯小球被反磁化产生相互吸引而形成短链的快过程以及短链间相互吸引形成长链的慢过程; 当外加磁场的方向垂直于样品平面时, 相邻聚苯乙烯小球表现出排斥的相互作用而形成短程有序的二维结构, 当磁场强度增加到一定的阈值时, 聚苯乙烯小球和磁性纳米颗粒形成的团簇会产生相互吸引而组装成复合式的花瓣结构. 关键词： 磁性液体 磁组装 非磁性颗粒     

面心立方铁纳米粒子的相变与并合行为的分子动力学研究

本文采用分子动力学模拟结合Finnis-Sinclair多体势研究了面心立方铁纳米粒子在加温过程中的相变与并合行为. 模拟结果表明: 纳米粒子在熔化之前均发生了由面心立方至体心立方的马氏体相变; 大小相等的两纳米粒子在并合之前发生了相对转动; 而大小不等的两纳米粒子在并合过程中并未出现转动, 小纳米粒子倾向于吸附在大纳米粒子上, 并随着温度的升高而熔化, 最终形成更大的纳米粒子. 关键词： 纳米粒子 相变 并合 分子动力学     

不同间距的钴纳米粒子一维链的制备及磁性能研究

在室温条件下用简单、易操作的方法磁诱导自组装制备出钴纳米粒子一维链状结构,研究了工艺条件对钴链中粒子的大小以及间距的影响.重点分析了两种不同粒径及间距的钴纳米粒子链状结构的磁性与温度的变化关系,发现钴纳米粒子链状结构在室温时呈超顺磁性,而在10K时呈弱铁磁性.提出了间距长（约10nm左右）的纳米链更趋近于单个纳米粒子的...     

In Situ Dimensional Characterization of Magnetic Nanoparticle Clusters during Induction Heating

The study and fundamental understanding of magnetic nanoparticle induction heating remains critical for the advancement of magnetic hyperthermia technologies. Complete characterization of not only the nanoparticles themselves but their interparticle behavior in a sample matrix is necessary to accurately predict their heating response. Herein, an in situ method for measuring the extent of nanoparticle clustering during induction heating using small-angle and ultrasmall-angle neutron scattering facilities at the National Institute of Standards and Technology Center for Neutron Research is described and implemented by comparing two sets of iron oxide nanoparticles with differing structures and magnetic properties. By fitting the scattering profiles to a piecewise model covering a wide Q-range, the magnitude of nanoparticle clustering during induction heating is quantified. Observations of the low-Q intensity before and after heating also allow for relative measurement of the cluster volume fraction during heating. The use of this method can prove to be advantageous in both developing more encompassing models to describe magnetic nanoparticle dynamics during heating as well as optimizing nanoparticle synthesis techniques to reduce aggregation during heating.     

Magnetic Nanoparticle Thermometry via Controlled Diffusion

The process of magnetic nanoparticle heating releases enormous amounts of thermal energy. Through typical calorimetric analyses, the total thermal energy released can be easily quantified; however, knowledge of nanoscale temperature is necessary. Herein, a novel method of nanoscale thermometry by analyzing intra-particle diffusion in core–shell nanoparticles is proposed. Heating the iron cores with an alternating magnetic field in a saline suspension encourages the diffusion of sodium ions into the silica shells of the particles, which is modeled numerically; however, experimental measurements are needed in order to provide accurate diffusivity estimations. After determining the diffusion characteristics from X-ray photoelectron spectroscopy) depth profiling of silica films, energy dispersive analysis with high-resolution transmission electron microscopy measures the sodium ion gradient within single particles before and after heating. When compared directly to the numerical simulations, the results indicate that the temperature gradient between particles and saline suspension reaches significantly higher temperatures than the macro-scale temperature of the solution. By accurately knowing the thermal gradient between nanoparticles and the surrounding medium, nanoparticles can be engineered to limit surface resistances as much as possible and promote high rates of thermal energy transfer.     

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.     

Scaling of transverse nuclear magnetic relaxation due to magnetic nanoparticle aggregation

The aggregation of superparamagnetic iron oxide (SPIO) nanoparticles decreases the transverse nuclear magnetic resonance (NMR) relaxation time of adjacent water molecules measured by a Carr-Purcell-Meiboom-Gill (CPMG) pulse-echo sequence. This effect is commonly used to measure the concentrations of a variety of small molecules. We perform extensive Monte Carlo simulations of water diffusing around SPIO nanoparticle aggregates to determine the relationship between and details of the aggregate. We find that in the motional averaging regime scales as a power law with the number N of nanoparticles in an aggregate. The specific scaling is dependent on the fractal dimension d of the aggregates. We find for aggregates with d=2.2, a value typical of diffusion limited aggregation. We also find that in two-nanoparticle systems, is strongly dependent on the orientation of the two nanoparticles relative to the external magnetic field, which implies that it may be possible to sense the orientation of a two-nanoparticle aggregate. To optimize the sensitivity of SPIO nanoparticle sensors, we propose that it is best to have aggregates with few nanoparticles, close together, measured with long pulse-echo times.     

A thermo-fluid analysis in magnetic hyperthermia

In the last years, hyperthermia induced by the heating of magnetic nanoparticles （MNPs） in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method （FEM） simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.     

Heat generation of aqueously dispersed CoFe2O4 nanoparticles as heating agents for magnetically activated drug delivery and hyperthermia

Self-heating from magnetic nanoparticles under AC magnetic field can be used either for hyperthermia or to trigger the release of an anti-cancer drug, using thermo-responsive polymers. The heat generated by applying an AC magnetic field depends on the properties of magnetic nanoparticles (composition, size, crystal structure) as well as the frequency and amplitude of the magnetic field. Before these systems can be efficiently applied for in vitro or in vivo studies, a thorough analysis of the magnetically induced heating is required. In this study, CoFe₂O₄ nanoparticles were synthesized, dispersed in water, and investigated as heating agents for magnetic thermo-drug delivery and hyperthermia. The temperature profiles and infrared (IR) camera images of heat generation of CoFe₂O₄ nanoparticles under various AC magnetic fields of 127–700 Oe at 195, 231, and 266 kHz were measured using an IR thermacam, excluding the external AC magnetic field interruption. The CoFe₂O₄ nanoparticles were successfully dispersed in water using an 11-mercaptoundecanoic acid ligand exchange method to exchange the solvent used for synthesis of hexane for water. During the heating experiments, each of CoFe₂O₄ nanoparticle solutions reached a steady state where the temperature rose between 0.1 and 42.9 °C above ambient conditions when a magnetic field of 127–634 Oe was applied at 231 or 266 kHz. The heat generation was found to be dependent on the intensity of AC magnetic field and applied frequency. Therefore, the desired heating for magnetically triggered drug delivery or hyperthermia could be achieved in water-dispersed CoFe₂O₄ nanoparticles by adjusting the AC magnetic field and frequency.     

Comparison between experimental and predicted specific absorption rate of functionalized iron oxide nanoparticle suspensions

Radio-frequency heated magnetic nanoaparticle suspensions have potential applications in cancer hyperthermia. To optimize these systems for hyperthermia applications it is important to be able to predict how their heat generation or specific absorption rate (SAR) is influenced by various factors, including nanoparticle coating or functionalization and aggregation. However, at present it is unclear how well-existing models predict experimental SAR results. Direct comparisons between predicted and measured SAR are scarce, despite an abundance of works reporting on heat generation rate of various magnetic nanoparticles suspensions. The main objective of this paper is to experimentally assess the validity of current models for SAR and extract information on the effects of coating and aggregation on heat generation rate. In this context, AC susceptibility and magnetization of suspensions of uncoated particles, as well as particles with aminosilane and carboxymethyl-dextran functionalizations, were measured. These properties were then used to predict the heat generation rate in alternating magnetic field starting from first principles, which was then compared to measured SAR. It was found that experimental SAR agrees relatively well with predictions (by a factor of two) when using experimental susceptibility values for the SAR calculation. However, for uncoated and amine-functionalized particles poor agreement (more than an order of magnitude difference) was found when the experimental susceptibility was substituted with predictions based on the Debye model. This apparent discrepancy is attributed to dipolar interactions between nanoparticles within aggregates in these samples, which enhances the imaginary part of the susceptibility and, consequently, the SAR values. The results also suggest that the thermal resistance effect of the coating has little influence on the SAR.     

Magnetic nanoparticle-based cancer therapy

Nanoparticles(NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles(MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging(MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.     

Heating in the MRI environment due to superparamagnetic fluid suspensions in a rotating magnetic field

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. 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 degree Centigrade 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 (approximately 1 cm 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 selection of the rotating or sinusoidal field parameters (field frequency and amplitude). The work indicates that it may be feasible to combine low-field MRI with a magnetic hyperthermia system using superparamagnetic iron oxide nanoparticles.     

Magnetic particle hyperthermia—biophysical limitations of a visionary tumour therapy

Loss processes being relevant for magnetic particle hyperthermia are analysed with respect to specific loss power under the condition of a limitation of the alternating magnetic field amplitude and frequency. Extrapolations to the maximum specific loss power of magnetic nanoparticles are discussed and conclusions are drawn with respect to the minimum particle concentration being necessary for hyperthermia or thermoablation under intra-tumoural or systemic particle supply. As a result, much efforts are necessary to render magnetic particle hyperthermia a valuable tumour therapy keeping at least part of the promises found in literature.