Three-Dimensional Model for Determining Inhomogeneous Thermal Dosage in a Liver Tumor During Arterial Embolization Hyperthermia Incorporating Magnetic Nanoparticles

Hyperthermia treatment incorporating magnetic nanoparticles (MNPs) is a hopeful therapy for cancers. Acquiring information about the MNPs' deposition in tumor tissues and modeling magnetic heating in vivo are essential for successful treatment. In this paper, we discuss the inhomogeneous heat generation by MNPs distributed heterogeneously in a liver tumor during arterial embolization hyperthermia (AEH) treatments. In order to more accurately simulate the temperature elevation for an AEH treatment plan, we conducted the following experiments. First, we detected the distribution of magnetic field intensity in the aperture of a ferrite-core applicator. We found that attenuation of the magnetic field focuses mainly on the vertical distance of the aperture, which makes MNPs in tissues have different power loss along the lognitudinal axis. Second, we prepared 20 nm monodisperse lipiodol-soluble MNPs and injected super-selectively through the micro-catheter into the arteries of a rabbit with a VX-2 liver tumor. By histological cuts of the investigated specimen, as well as computed tomography (CT), we found MNPs mainly concentrated on the tumor periphery. Last, from the experimental information, we established a new model for simulating the increasing temperature in the liver tumor based on our inhomogeneous interior-heat-source analysis (IIA). We also compared the simulated results with the two types of homogeneous models. The results showed that IIA gives significantly different results from those for a homogeneous model and thus is preferable when an accurate treatment plan is required during AEH.      

Numerical study of temperature distribution in a spherical tissue in magnetic fluid hyperthermia using lattice Boltzmann method

This work applies a three-dimensional lattice Boltzmann method (LBM), to solve the Pennes bio-heat equation (BHE), in order to predict the temperature distribution in a spherical tissue, with blood perfusion, metabolism and magnetic nanoparticles (MNPs) heat sources, during magnetic fluid hyperthermia (MFH). So, heat dissipation of MNPs under an alternating magnetic field has been studied and effect of different factors such as induction and frequency of magnetic field and volume fraction of MNPs has been investigated. Then, effect of MNPs dispersion on temperature distribution inside tumor and its surrounding healthy tissue has been shown. Also, effect of blood perfusion, thermal conductivity of tumor, frequency and amplitude of magnetic field on temperature distribution has been explained. Results show that the LBM has a good accuracy to solve the bio-heat transfer problems.     

Thermal analysis in the rat glioma model during directly multipoint injection hyperthermia incorporating magnetic nanoparticles

Hyperthermia incorporating magnetic nanoparticles (MNPs) is a hopeful therapy to cancers and steps into clinical tests at present. However, the clinical plan of MNPs deposition in tumors, especially applied for directly multipoint injection hyperthermia (DMIH), and the information of temperature rise in tumors by DMIH is lack of studied. In this paper, we mainly discussed thermal distributions induced by MNPs in the rat brain tumors during DMIH. Due to limited experimental measurement for detecting thermal dose of tumors, and in order to acquire optimized results of temperature distributions clinically needed, we designed the thermal model in which three types of MNPs injection for hyperthermia treatments were simulated. The simulated results showed that MNPs injection plan played an important role in determining thermal distribution, as well as the overall dose of MNPs injected. We found that as injected points enhanced, the difference of temperature in the whole tumor volume decreased. Moreover, from temperature detecting data by Fiber Optic Temperature Sensors (FOTSs) in glioma bearing rats during MNPs hyperthermia, we found the temperature errors by FOTSs reduced as the number of points injected enhanced. Finally, the results showed that the simulations are preferable and the optimized plans of the numbers and spatial positions of MNPs points injected are essential during direct injection hyperthermia.     

Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia

Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42?°C) or damage (<42 °C) depending on the localized rise in temperature. We investigated the therapeutic effect of MFH in immortalized T lymphocyte (Jurkat) cells using monodisperse magnetite (Fe(3)O(4)) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ～16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe(3)O(4)) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application.     

A novel magnetic nanoparticle hyperthermia combined with ACMF-dependant drug release by DAMMs injection in VX-2 liver tumors

In this paper, we investigated the feasibility and effect of a novel combination therapy of magnetic nanoparticles (MNPs) hyperthermia with anticancer drugs for solid malignancies using doxorubicin-loaded alginate-templated magnetic microcapsules (DAMMs) in an animal liver cancer model. Firstly, DAMMs containing 18 nm gamma-Fe2O3 with doxorubicin (Dox) were synthesized and characterized. Then, the particular behavior of Dox release under external alternating current magnetic filed (ACMF) was tested in vitro. Moreover, to obtain accurate thermotherapy, the dose of DAMMs and temperature rise were computed by Hyperthermia treatment plan (HTP) and a fiber optic temperature sensor (FOTS) was used to monitor the temperature rise during treatments on VX-2 liver tumor-bearing rabbits. Furthermore, the therapeutic effect was studied by histopathological examinations and animal survival. The results showed that ACMF can induce Dox fast release during the treatment and the high MNPs content of DMMAs guaranteed the temperature rise for hyperthermia in tumors. The rabbits bearing VX-2 tumors in the magnetic hyperthermia using DMMAs group gained the most tumor necrosis and survival time. It was indicated that DAMMs-based magnetic hyperthermia could be a feasible and effective remedy which could be targeted at liver tumors by dual effects of hyperthermia and chemotherapy.     

Minimal-invasive magnetic heating of tumors does not alter intra-tumoral nanoparticle accumulation, allowing for repeated therapy sessions: an in vivo study in mice

Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles (MNPs) continue to be an active area of cancer research. For generating the appropriate heat to sufficiently target cell destruction, adequate MNP concentrations need to be accumulated into tumors. Furthermore, the knowledge of MNP bio-distribution after application and additionally after heating is significant, firstly because of the possibility of repeated heating treatments if MNPs remain at the target region and secondly to study potential adverse effects dealing with MNP dilution from the target region over time. In this context, little is known about the behavior of MNPs after intra-tumoral application and magnetic heating. Therefore, the present in vivo study on the bio-distribution of intra-tumorally injected MNPs in mice focused on MNP long term monitoring of pre and post therapy over seven days using multi-channel magnetorelaxometry (MRX). Subsequently, single-channel MRX was adopted to study the bio-distribution of MNPs in internal organs and tumors of sacrificed animals. We found no distinct change of total MNP amounts in vivo during long term monitoring. Most of the MNP amounts remained in the tumors; only a few MNPs were detected in liver and spleen and less than 1% of totally injected MNPs were excreted. Apparently, the application of magnetic heating and the induction of apoptosis did not affect MNP accumulation. Our results indicate that MNP mainly remained within the injection side after magnetic heating over a seven-days-observation and therefore not affecting healthy tissue. As a consequence, localized magnetic heating therapy of tumors might be applied periodically for a better therapeutic outcome.     

FePtAg-C纳米颗粒薄膜的制备及表征

采用磁控溅射法在硅基片上生长FePt纳米颗粒薄膜。在硅片表面生长MgO籽层用来引发FePt合金薄膜的fct织构,加入C来减小其颗粒尺寸,加入Ag来增强其L10有序度。采用X射线衍射仪（XRD）、超导量子干涉仪（SQUID）和高分辨率透射电镜（TEM）对FePt薄膜进行表征。结果表明制备的薄膜样品具有优良的L10相结构,其M-H曲线表明方形度很好,垂直矫顽力HC有2467 kA/m,颗粒大小为10.4 nm。该薄膜非常适合用做下一代高密度磁存储媒质,可有效提高信息存储密度。     

Real‐Time Analysis of Magnetic Hyperthermia Experiments on Living Cells under a Confocal Microscope

Combining high‐frequency alternating magnetic fields (AMF) and magnetic nanoparticles (MNPs) is an efficient way to induce biological responses through several approaches: magnetic hyperthermia, drug release, controls of gene expression and neurons, or activation of chemical reactions. So far, these experiments cannot be analyzed in real‐time during the AMF application. A miniaturized electromagnet fitting under a confocal microscope is built, which produces an AMF of frequency and amplitude similar to the ones used in magnetic hyperthermia. AMF application induces massive damages to tumoral cells having incorporated nanoparticles into their lysosomes without affecting the others. Using this setup, real‐time analyses of molecular events occurring during AMF application are performed. Lysosome membrane permeabilization and reactive oxygen species production are detected after only 30 min of AMF application, demonstrating they occur at an early stage in the cascade of events leading eventually to cell death. Additionally, lysosomes self‐assembling into needle‐shaped organization under the influence of AMF is observed in real‐time. This experimental approach will permit to get a deeper insight into the physical, molecular, and biological process occurring in several innovative techniques used in nanomedecine based on the combined use of MNPs and high‐frequency magnetic fields.     

Magnetite nanoparticles with high heating efficiencies for application in the hyperthermia of cancer

Magnetic hyperthermia is a safe method for cancer therapy. A gap-type alternating current magnetic field (100 kHz, 100–300 Oe) is expected to be clinically applicable for magnetic hyperthermia. In this study, magnetite nanoparticles (MNPs) varying in size from 8 to 413 nm were synthesized using a chemical coprecipitation and an oxidation precipitation method to find the optimum particle size that shows a high heating efficiency in an applied magnetic field. The particles' in vitro heating efficiency in an agar phantom at an MNP concentration of 58 mg Fe/ml was measured in an applied magnetic field. In a magnetic field of 120 Oe, the temperature increase (ΔT) of the agar phantom within 30 s was 9.3 °C for MNPs with a size of 8 nm, but was less for the other samples, while in a magnetic field of 300 Oe, ΔT = 55 °C for MNPs with a size of 24 nm, and ΔT = 25 °C for MNPs with a size of 8 nm. The excellent heating efficiency of MNPs with a size of 24 nm in a magnetic field of 300 Oe may be due to a combination of the effects of both relaxation and hysteresis losses of the magnetic particles. It is believed that MNPs with a size of 8–24 nm will be useful for the in situ hyperthermia treatment of cancer.     

FePt nanocluster films for high-density magnetic recording

High anisotropy L1(0) ordered FePt thin films are considered to have high potential for use as high areal density recording media, beyond 1 Tera bit/in2. In this paper, we review recent results on the synthesis and magnetic properties of L1(0) FePt nanocomposite films. Several fabrication methods have been developed to produce high-anisotropy FePt films: epitaxial and non-epitaxial growth of (001)-oriented FePt:X (X = Au, Ag, Cu, C, etc.) composite films that might be used for perpendicular media; monodispersed FePt nanocluster-assembled films grown with a gas-aggregation technique and having uniform cluster size and narrow size distribution; self-assembled FePt particles prepared with chemical synthesis by reduction/decomposition techniques, etc. The magnetic properties are controllable through variations in the nanocluster properties and nanostructure. FePt and related films show promise for development as heat-assisted magnetic recording media at extremely high areal densities. The self-assembled FePt arrays show potential for approaching the ultimate goal of single-grain-per-bit patterned media.     

High-density perpendicular magnetic recording media of granular-type (FePt/MgO)/soft underlayer

Perpendicular magnetic recording media, composed of granular-type FePt-MgO films on Fe-Ta-C soft magnetic underlayer (SUL), have been fabricated on to 2.5-in glass disks. [001] textured FePt granular films with high-perpendicular magnetic anisotropy were obtained by annealing the FePt/MgO multilayer films. The FePt grain size, perpendicular coercivity, magnetic activation volume, and the exchange coupling between the FePt grains were found to be strongly dependent on the initial multilayer structures and the annealing conditions. The recording performance of the disks was evaluated by a spin-stand. The obtained results reveal a close correlation between the recording performance and magnetic properties. The thermal stability of the granular-type FePt media was studied using high-temperature magnetic force microscopy (MFM) technique, equipped with in situ sample heating, in the temperature range 25/spl deg/C-200/spl deg/C. The estimated signal decay at high temperature is ascribed to the temperature dependent magnetic anisotropy behavior.     

FePt and CoPt nanoparticles co-deposited on silicon dioxide-a comparative study

We compare CoPt and FePt nanoparticles grown under identical conditions on oxidized Si?substrates by electron beam co-evaporation. Growth was performed under high vacuum conditions at substrate temperatures of 1023?K and was immediately followed by an annealing step. This process forms CoPt and FePt nanoparticles with mean diameters between ～17 and ～22?nm. In particular, the annealing step results in grain size enlargement for all samples and in a progressive magnetic hardening of the nanoparticles which reach maximum perpendicular coercivities of ～6.6?kOe (for the CoPt) and ～10.2?kOe (for the FePt nanoparticles). We show that, during this annealing step, a progressive transition towards the hard magnetic L1(0) ordered phase takes place in both materials. In contrast to FePt, CoPt nanoparticles must be annealed in order to crystallize in this phase.     

Design of a carbon nanotube/magnetic nanoparticle-based peroxidase-like nanocomplex and its application for highly efficient catalytic oxidation of phenols

We report a novel nanotechnology-based approach for the highly efficient catalytic oxidation of phenols and their removal from wastewater. We use a nanocomplex made of multi-walled carbon nanotubes (MWNTs) and magnetic nanoparticles (MNPs). This nanocomplex retains the magnetic properties of individual MNPs and can be effectively separated under an external magnetic field. More importantly, the formation of the nanocomplex enhances the intrinsic peroxidase-like activity of the MNPs that can catalyze the reduction of hydrogen peroxide (H₂O₂). Significantly, in the presence of H₂O₂, this nanocomplex catalyzes the oxidation of phenols with high efficiency, generating insoluble polyaromatic products that can be readily separated from water.      

Onset of hard magnetic L10 FePt phase with (001) texture

The perpendicular anisotropic magnetic properties of in-situ deposited FePt/Pt/Cr trilayer films were elucidated as functions of the deposition temperature and the sputtering rate of the FePt magnetic layer. Ordered L1₀ FePt thin films with perpendicular anisotropy and a (001) texture can be developed at a temperature as low as 300 °C with the sputtering of a FePt layer at a low rate. The larger Pt(001)[100] lattice induced an expansion of the FePt a- and b-axis, leading to the contraction of the FePt c-axis, enabling the epitaxial growth of the L1₀ FePt(001) texture to occur. A low rate of sputtering of the FePt thin film promotes the formation of the magnetically hard FePt(001) texture on the surface of the Pt(001) buffer layer at low temperature, while the high sputtering rate of FePt layer suppresses the phase transformation.     

Wrap-bake-peel process for nanostructural transformation from beta-FeOOH nanorods to biocompatible iron oxide nanocapsules

The thermal treatment of nanostructured materials to improve their properties generally results in undesirable aggregation and sintering. Here, we report on a novel wrap-bake-peel process, which involves silica coating, heat treatment and finally the removal of the silica layer, to transform the phases and structures of nanostructured materials while preserving their nanostructural characteristics. We demonstrate, as a proof-of-concept, the fabrication of water-dispersible and biocompatible hollow iron oxide nanocapsules by applying this wrap-bake-peel process to spindle-shaped akagenite (beta-FeOOH) nanoparticles. Depending on the heat treatment conditions, hollow nanocapsules of either haematite or magnetite were produced. The synthesized water-dispersible magnetite nanocapsules were successfully used not only as a drug-delivery vehicle, but also as a T2 magnetic resonance imaging contrast agent. The current process is generally applicable, and was used to transform heterostructured FePt nanoparticles to high-temperature face-centred-tetragonal-phase FePt alloy nanocrystals.     

Thermochemotherapy mediated by novel solar-planet structured magnetic nanocomposites for glioma treatment

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. This work evaluates the effects of a kind of novel solar-planet structured magnetic nanocomposites (MNCs) for magnetic thermochemotherapy. Amino silane coated magnetic nanoparticles (MNPs) as agent of magnetic mediated hyperthermia (MMH) for cancer treatment were prepared by the chemical precipitation method. Docetaxel (an anticancer drug) loaded polymeric nanoparticles (DNPs) composed of carboxylic-terminated poly (D,L-lactic-co-glycolic acid) (PLGA) with Vitamin E TPGS as emulsifier for sustained drug release were prepared by a modified solvent extraction/evaporation technique. Furthermore, the MNPs modified with amino groups could be covalently attached to the surface of carboxylic terminated DNPs to form the so-called solar-planet structured MNCs by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking. The prepared solar-planet structure has been confirmed by fluorescent observation. Inductive heating property of the nanocomposite was evaluation by monitoring the temperature increase of the MNCs suspension under alternative magnetic field (AMF). Drug encapsulation efficacy and drug release of the magnetic nanocomposite were conducted by high performance liquid chromatography (HPLC). In vitro evaluation of the novel nanocomposite as mediator for thermochemotherapy was conducted on the U251 human glioma cells and the synergistic effect between MMH and docetaxel chemotherapy was confirmed. All the observation supports that solar-planet structured MNC is a novel and effective mediator for magnetic thermochemotherapy. The MNCs can realize cancer comprehensive treatment thus has great potential in clinical application.     

Sintering Effect of Annealed FePt Nanocrystal Films Observed by Magnetic Force Microscopy

Chemically synthesized FePt nanocrystals can exhibit room temperature ferromagnetism after being annealed at temperatures above 500degC. In thick films composed of FePt nanocrystals, the coercivity can be quite large. However, the coercivity of thin films has been found to decrease significantly with decreasing thickness, to the point that ferromagnetism at room temperature is lost. We studied 12 to 55 nm thick films by using magnetic force microscopy (MFM) under external applied fields. We made smooth films by spin casting 4-nm-diameter FePt nanocrystals and annealing them at 605degC-630degC. Thin FePt films showed lower coercivity than thick films. To help interpret the MFM images, we obtained complementary magnetic and structural data by superconducting quantum interference device (SQUID) magnetometry, transmission electron microscopy (TEM), and X-ray diffraction. We conclude that the magnetic properties of these films are strongly affected by nanocrystal aggregation that occurs during annealing     

Spherical porous hydroxyapatite granules containing composites of magnetic and hydroxyapatite nanoparticles for the hyperthermia treatment of bone tumor

Spherical porous granules of hydroxyapatite (HA) containing magnetic nanoparticles would be suitable for the hyperthermia treatment of bone tumor, because porous HA granules act as a scaffold for bone regeneration, and magnetic nanoparticles generate sufficient heat to kill tumor cells under an alternating magnetic field. Although magnetic nanoparticles are promising heat generators, their small size makes them difficult to support in porous HA ceramics. We prepared micrometer-sized composites of magnetic and HA nanoparticles, and then supported them in porous HA granules composed of rod-like particles. The spherical porous HA granules containing the composites of magnetic and HA nanoparticle were successfully prepared using a hydrothermal process without changing the crystalline phase and heat generation properties of the magnetic nanoparticles. The obtained granules generated sufficient heat for killing tumor cells under an alternating magnetic field (300 Oe at 100 kHz). The obtained granules are expected to be useful for the hyperthermia treatment of bone tumors.     

Tumour cell toxicity of intracellular hyperthermia mediated by magnetic nanoparticles

Intracellular hyperthermia is a process by which malignant cells can be selectively killed by heat generated by nanomediators located inside the cell. Here we show that maghemite anionic nanoparticles are efficiently captured by human prostatic tumor cells (PC3) and concentrate within intracellular vesicles. When submitted to an alternative magnetic field, maghemite nanocrystals generate heat from the cell inside, inducing a temperature elevation of eight degree in a loose pellet of 20 million magnetically labeled cells. We demonstrate that this heating modality was as lethal as external waterbath heating. A one hour AC magnetic field (700 kHz-31 mT) exposure of the magnetically labeled cells killed 44% of the cells. Interestingly, more than 80% of the cells were killed after being submitted twice to the magnetic field. Finally, when magnetic cells coexist with non magnetic ones, the same proportions of cells were damaged for both populations, after magnetic field exposure. These findings pave the way for an efficient cell killing mediated by intracellular magnetic hyperthermia.     

Chemically synthesized FePt nanoparticle material for ultrahigh-density recording

We have examined the magnetic anisotropy of the "heat-treated FePt nanoparticles" annealed in a magnetic field. The magnetic easy axis of the "heat-treated FePt nanoparticles" is found to be three-dimensional (3-D) random and a partial ordering fct structure is observed before annealing in the presence of a magnetic field. The value of M/sub r//M/sub s/ obtained is 0.5. After annealing in the presence of a magnetic field, the M-H loop indicates that the easy axis is oriented preferably in the perpendicular direction than along the in-plane direction. The value of H/sub c/(//)/H/sub c/(/spl perp/) at 10 K is 0.62 (1410 Oe/2250 Oe). The value of M/sub r//M/sub s/(/spl perp/) is 0.58 at 10 K larger than the value of M/sub r//M/sub s/(//). Therefore, a weak magnetic easy axis orientation is fundamentally possible on the chemically synthesized FePt nanoparticles. We have studied the recording characteristics of a 3-D random nanoparticle medium using a GUZIK spinstand and observed the recorded patterns for the medium by imaging with a magnetic force microscopy.