磁性阿霉素纳米微球的制备及在高频磁场中的发热研究

制备一种在高频磁场中能感应发热的用于治疗肿瘤的阿霉素纳米微球，研究其在磁场中的热效应。用超声搅拌冷冻干燥的方法制备药物微球，平均粒径200nm左右。电镜观察其形态为球囊状。将其置于不同介质中于高频磁场中测其温度变化值，实验表明该微球在交变磁场中使介质升温。升温速度与平稳时的温度和微球的量及磁场强度成正比，介质流动性好，升温快。     

磁性阿霉素纳米微球在磁场中磁感应的发热研究

目的：制备一种在高频磁场中能感应发热的用于治疗肿瘤的阿霉素纳米微球，研究其在磁场中的热效应。材料与方法：用超声搅拌冷冻干燥的方法制备药物微球，电镜观察其形态及粒径估测。将其置于不同介质中于高频磁场中测其温度变化值。结果：磁性阿霉素微球为球囊状，平均粒径200nm左右，最小为150nm，最大为350nm，该微球在交变磁场中使介质升温。升温速度与平稳时的温度和微球的量，磁场强度成正比，介质流动性好，升温快。结论：可通过调节磁场强度和磁性阿霉素微球的量使周围温度达到所需值。     

交变磁场诱导冠状动脉支架的升温

背景:对于药物涂层支架的安全性问题目前尚存在争议。磁诱导热疗可以利用交变磁场诱导磁介质升温,对局部病灶进行热疗。由于心脏支架多以不锈钢、镍、铬等合金材料构成,因此具备在磁场下的升温条件,并且目前国内外尚无通过磁诱导心脏支架升温的相关报道。目的:观察不同冠状动脉支架在交变磁场下的升温情况。探讨磁场强度、磁场频率、磁场方向及支架的材质对冠状动脉支架升温的影响规律。方法:将不同材质冠状动脉支架(316L型、镍钛合金、钴铬合金)置于交变磁场中,调节磁场参数(场强、频率)和支架长轴与磁场方向的夹角,观察上述因素对交变磁场诱导冠状动脉支架升温的影响。结果与结论:支架材料对磁场诱导升温有显著影响,并以316L型支架升温效果最好;随着支架长轴与磁场方向所成角度的增大,升温效果明显降低;随着交变磁场频率及电流强度增加温度升高更明显。     

具有磁感应定向加热治疗肿瘤作用的锰锌铁氧体纳米粒子的制备及其特性检测

采用改良的化学共沉淀法制备Mn0.5Zn0.5Fe2O4纳米磁性材料，用透射电镜、分析仪及热分析系统等进行表征及特性检测。将Mn0.5Zn0.5Fe2O4纳米粒子以及其不同浓度的磁流体置于200KHz的交变磁场中照射，检测其磁感应自控加热作用；用Mn0.5Zn0.5；Fe2O4浸渍液体外干预小鼠L929成纤维细胞，通过检测细胞增值率来评价其细胞毒性。结果表明，制备的锰锌铁氧体纳米粒子为圆形，约40nm，并经检索X-线粉末衍射图库证实；纳米锰锌铁氧体磁流体能磁感应加热而升温到40℃～51℃，且最终温度能稳定控制不变；纳米锰锌铁氧体浸渍液对细胞未见明显毒性作用。     

微米级羰基铁粉磁性骨水泥的制备与表征

背景：目前有日本学者提出采用磁性骨水泥治疗肿瘤的骨转移,然而现行磁性骨水泥添加的均为纳米级磁流体,将微米级羰基铁粉添入骨水泥的研究尚未见报道。 目的：制备含不同比例微米级羰基铁粉的磁性骨水泥,并按ISO 5833标准测量相关指标及其磁性与体外升温情况。 方法：将微米级羰基铁粉与聚甲基丙烯酸甲酯骨水泥混合制备成含羰基铁粉质量分数分别为0%,20%,30%,40%,50%的磁性骨水泥。将以上5组材料按ISO 5833标准测定凝固时间、聚合温度、抗压强度。并采用振动样品磁强计测定各组磁性及在交变磁场下的升温情况。 结果与结论：随着羰基铁粉含量的增加,磁性聚甲基丙烯酸甲酯骨水泥的凝固时间有所延长。各组骨水泥的最高聚合温度均在65-70 ℃之间,并未随羰基铁粉含量的增加而改变,仅聚合温度最高点出现的时间随羰基铁粉含量提高而后延。各组骨水泥的抗压能力均大于60 MPa,但只有聚甲基丙烯酸甲酯骨水泥的抗压能力＞70 MPa,符合IOS 5833标准要求。各组磁性骨水泥的磁饱和强度随羰基铁粉含量的提高而提高。在交变磁场下,磁性骨水泥的升温速率与磁场强度和羰基铁粉含量呈正相关。     

用于微循环实验的交变磁场的三维有限元仿真研究

目的:为深入了解螺线管型交变电磁场磁感应强度的时间和空间分布,本文研究了这种微循环实验中常用的医用磁场的三维有限元模型的建立及分析过程.方法:根据经典电磁场理论,应用Comsol Multiphysics多物理场耦合软件进行计算机辅助设计并赋予模型边界条件后进行网格划分,最后得到该模型的数值解.结果:成功拟合出螺线管型交变电磁场磁感应强度的轴向和径向衰减曲线.拟合结果与实际情况近似,并算出交变电磁场的时空分布.结论:本研究首次系统的建立了螺线管型交变电磁场的三维有限元模型,能够较精确的模拟该磁场磁感应强度分布,为进一步进行的磁场影响微循环系统的实验中磁场的定位问题提供了理论依据,并为进行血流在不同磁场中的血液动力学研究建立了仿真平台.     

抗HSA与微晶纤维素的固定化

采用溴化氰化学修饰法制备抗HSA－微晶纤维素固相抗体，对制备条件进行了优化，以修饰温度20℃、抗体浓度3．5mg/mL为固定化最佳条件；并对固相抗体进行了扫描电镜测定、稳定性考察及初步应用。     

磁场对荷瘤小鼠免疫功能的影响

本文研究了低频交变磁场和稳恒磁场对荷瘤小鼠免疫功能的影响。实验结果表明，磁场强度为１５ｍＴ的５０Ｈｇ交变磁场和８０ｍＴ的稳恒磁场均能提高机体的免疫功能；对肿瘤组织的供血情况有明显抑制效果，且磁场使肿瘤组织内形成较丰富的间质纤维，使肿瘤细胞坏死明显增多。     

离体胎骨的超声热效应

离体胎骨(其上所有软组织已被完全剔除)在37℃温度下,受到频率为1MHz的连续超声波辐照后温度上升。在实验中,用热电偶对几个不同胎令的胎儿股骨的升温进行了测量,并与已知的软组织超声吸     

铁磁颗粒诱导加温治疗恶性肿瘤的研究进展

铁磁颗粒通过特定方法导入肿瘤区域后在交变磁场下可以升温至41.0℃以上,从而杀死肿瘤细胞,此种加温治疗肿瘤方法的特异性和高度靶向性是其它加温方法无法比拟的,近年来,此方面的研究越来越受到广大学者的关注,本文就铁磁颗粒加温治疗恶性肿瘤的研究进展加以简要介绍.     

TC-tuned biocompatible suspension of La0.73Sr0.27MnO3 for magnetic hyperthermia

La(1-x)Sr(x)MnO(3), a ferromagnet with high magnetization and Curie temperature T(C) below 70 degrees C, enables its use for magnetic hyperthermia treatment of cancer with a possibility of in vivo temperature control. We found that La(0.73)Sr(0.27)MnO(3) particles of size range 20-100 nm showed saturation magnetization around 38 emu/g at 20 kOe and a T(C) value of 45 degrees C. Aqueous suspension of these nanoparticles was prepared using a polymer, acrypol 934, and the biocompatibility of the suspension was examined using HeLa cells. A good heating ability of the magnetic suspension was obtained in the presence of AC magnetic field, and it was found to increase with the amplitude of field. The suspension having concentration of 0.66 mg/mL (e.g., 0.66 mg of nanoparticles with acropyl per milliliter of culture media) was observed to be biocompatible even after 96 h of treatment, as estimated by sulforhodamine B and trypan blue dye exclusion assays. Further, the treatment with the aforementioned concentration did not alter the microtubule cytoskeleton or the nucleus of the cells. However, the bare particles (concentration of 0.66 mg of nanoparticles per milliliter of culture media, but without acropyl) decreased the viability of cell significantly. Our in vitro studies suggest that the suspension (concentration of 0.66 mg/mL) may further be analyzed for in vivo studies.     

Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression

One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field (AMF) was used to activate gene expression. MZF-NPs, obtained by co-precipitation method, were firstly surface modified with cation poly(ethylenimine) (PEI). Then thermodynamic test of various doses of MZF-NPs was preformed in vivo and in vitro. PEI-MZF-NPs showed good DNA binding ability and high transfection efficiency. In AMF, they could rise to a steady temperature. To analyze the heat-induced gene expression under an AMF, we combined P1730OR vector transfection with hyperthermia produced by irradiation of MZF-NPs. By using LacZ gene as a reporter gene and Hsp70 as a promoter, it was demonstrated that expression of a heterogeneous gene could be elevated to 10 to 500-fold over background by moderate hyperthermia (added 12.24 or 25.81 mg MZF-NPs to growth medium) in tissue cultured cells. When injected with 2.6 or 4.6 mg MZF-NPs, the temperature of tumor-bearing nude mice could rise to 39.5 or 42.8 degrees C, respectively, and the beta-gal concentration could increase up to 3.8 or 8.1 mU/mg proteins accordingly 1 day after hyperthermia treatment. Our results therefore supported hyperthermia produced by irradiation of MZF-NPs under an AMF as a feasible approach for targeted heat-induced gene expression. This novel system made use of the relative low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore acquired safe and effective heat-inducible transgene expression.     

Defining the heating characteristics of ferromagnetic implants using calorimetry

The induction heating of small, cylindrical ferromagnetic implants for localized tumors is currently under investigation. These thermal rods are implanted within a lesion in 1 cm(2) arrays and subsequently exposed to an externally applied alternating magnetic field. Implants absorb energy from the field and transfer it as heat to the surrounding tissue. To achieve a uniform temperature rise throughout the tissue volume and to account for any field-rod misalignment, 400 mW of power per implant is used as the design specification. The temperature to necrose cells must be greater than 46 degrees C. A calorimeter was constructed to confirm that the rod power output specification is satisfied at temperatures adequate for inducing cell death. The rods were designed to undergo a ferromagnetic to paramagnetic transition at temperatures of 55 degrees C, 60 degrees C, 65 degrees C, and 70 degrees C; this transition produces rods that are temperature self-regulating. Calorimetric results demonstrated that 55 degrees C, 60 degrees C, 65 degrees C, and 70 degrees C rods provided 400 mW at 47-51 degrees C, 51-53.5 degrees C, 57 degrees C, and 62.5-63.5 degrees C, respectively. Thermal rods provide sufficient power output at the temperatures necessary to cause thermal ablation of tumors. The higher-temperature rods give a greater margin to ensure that necrotizing temperatures can be achieved throughout the rod array even with minor misalignment.     

In vivo heating of magnetic nanoparticles in alternating magnetic field

We have evaluated heating capabilities of new magnetic nanoparticles. In in vitro experiments they were exposed to an alternating magnetic field with frequency 3.5 MHz and induction 1.5 mT produced in three turn pancake coil. In in vivo experiments rats with injected magnetic nanoparticles were also exposed to an ac field. An optimal increase of temperature of the tumor to 44 degrees C was achieved after 10 minutes of exposure. Obtained results showed that magnetic nanoparticles may be easily heated in vitro as well as in vivo, and may be therefore useful for hyperthermic therapy of cancer.     

The development of magnetic degradable DP-Bioglass for hyperthermia cancer therapy

In this study, a novel magnetic degradable material was developed by adding Fe ions into DP-Bioglass (Na(2)O-CaO-P(2)O(5)-SiO(2)) as thermoseed for hyperthermia cancer therapy under an alternating magnetic field. We have investigated the properties of developed magnetic DP-Bioglass including morphology, chemical composition, and magnetism. The degradability was conducted by measuring the released concentrations of Na, Ca, Si, P, and Fe ions. The biocompatibility was analyzed by biological assays, and the functional hyperthermia effect to cancer cells was evaluated by in vitro cell culture test. In the results, the morphology of synthesized magnetic DP-Bioglass was revealed in sphere and rod shape with particle size around 50-100 nm. From the hysteresis loop analysis, it showed that the group of Fe/Bioglass = 0.2 possessed the maximum magnetization property. When cultured with fibroblasts, the magnetic DP-Bioglass had no significant influence on cell viability and mediated low cytotoxicity. The thermal-induced property demonstrated that after exposure to an alternating magnetic field, the cell number of human Caucasian lung carcinoma cells (A549) was significantly decreased when temperature was increasing to 45 degrees C. In brief, successfully incorporated with Fe ions by sol-gel method, this magnetic degradable DP-Bioglass possessed the potential and properties of hyperthermia effect to lung carcinoma cells.     

Investigation on Tc tuned nano particles of magnetic oxides for hyperthermia applications

Superparamagnetic as well as fine ferrimagnetic particles such as Fe3O4, have been extensively used in magnetic field induced localized hyperthermia for the treatment of cancer. The magnetic materials with Curie temperature (Tc) between 42 and 50 degrees C, with sufficient biocompatibility are the best candidates for effective treatment such that during therapy it acts as in vivo temperature control switch and thus over heating could be avoided. Ultrafine particles of substituted ferrite Co(1-a)Zn(a)Fe2O4 and substituted yttrium-iron garnet Y3Fe(5-x)Al(x)O12 have been prepared through microwave refluxing and citrate-gel route respectively. Single-phase compounds were obtained with particle size below 100 nm. In order to make these magnetic nano particles biocompatible, we have attempted to coat these above said composition by alumina. The coating of alumina was done by hydrolysis method. The coating of hydrous aluminium oxide has been done over the magnetic particles by aging the preformed solid particles in the solution of aluminium sulfate and formamide at elevated temperatures. In vitro study is carried out to verify the innocuousness of coated materials towards cells. In vitro biocompatibility study has been carried out by cell culture method for a period of three days using human WBC cell lines. Study of cell counts and SEM images indicates the cells viability/growth. The in vitro experiments show that the coated materials are biocompatible.     

Hydrogel nanocomposites as remote-controlled biomaterials

Nanocomposite hydrogels are a new class of intelligent materials which have recently attracted interest as biomaterials. In this study, magnetic nanocomposites of temperature-sensitive hydrogels have been developed and demonstrated to be responsive to alternating magnetic fields. Nanocomposites were synthesized by incorporation of superparamagnetic Fe(3)O(4) particles in negative temperature-sensitive poly(N-isopropylacrylamide) hydrogels. The systems were characterized for temperature-responsive swelling, remote heating on application of an alternating magnetic field and remote-controlled drug delivery applications. The rise in temperature in external alternating magnetic field depends on the Fe(3)O(4) particle loading of the system. Preliminary studies on remote-controlled drug release showed reduced release in the presence of an alternating magnetic field.     

Bio‐Inspired Multiple Cycle Healing and Damage Sensing in Elastomer–Magnet Nanocomposites

Damage‐sensing and healing are biological functions which are urgently required in structural health monitoring and remediation of engineering structures. The development of a bio‐inspired multiple cycle damage sensing and triggered healing magnet–polymer nanocomposite (Magpol) is reported. Magpol is comprised of an acrylonitrile butadiene co‐polymer (NBR) matrix and a magnetic nanoparticle (MNP) filler. Magpol nanocomposites in a range of MNP filler concentrations are studied. NBR is selected as the matrix due to its extensive use in industrial coatings, for example, in the automotive industry. Mn‐Zn ferrite MNP is chosen due to its appropriate Curie temperature and good specific absorption rate. Exposure of damaged Magpol to a remote external alternating magnetic field results in MNP heating. The MNP heats the surrounding NBR matrix, resulting in triggered healing. Fractured Magpol samples are successfully healed over several cycles. Incorporation of rhodamine b mechano‐chromophore in Magpol results in multicycle damage sensing by photo‐luminescent absorption. Thus, the developed Magpol is attractive for structural health monitoring and remediation application.     

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia.