静磁场靶向药物递送系统在肿瘤诊疗中的研究进展

化疗是治疗肿瘤的传统手段之一,但其具有组织非特异性,在抑制肿瘤细胞生长的同时也会对正常细胞产生毒副作用.磁靶向药物递送系统可通过具有生物相容性的、稳定的磁性纳米颗粒载体将抗癌药物在外磁场的引导下,靶向运输和浓聚在肿瘤组织.该技术不仅提高了药物运输的效率和药物的抗癌活性,还能降低药物用量和减轻毒副作用.载药磁性纳米颗粒和所应用的外磁场的性质是影响磁性纳米颗粒靶向肿瘤组织的重要影响因素.载药磁性纳米颗粒的靶向递送是否有效,主要依赖靶向目标位置处所应用的磁场和磁场强度是否足够吸引束缚载药磁性纳米颗粒在肿瘤组织中停留以及释放.对静磁场在引导磁性纳米颗粒靶向肿瘤组织研究的新进展进行综述,为静磁场在靶向肿瘤治疗方面提供一定的科研基础支持.     

磁靶向定位灌注化疗膀胱癌磁性吡柔比星纳米粒的制备与评价

目的构建一种新型的磁靶向定位灌注化疗膀胱癌的吡柔比星纳米制剂,并探讨其磁靶向定位及抗膀胱癌细胞特性,为定位灌注化疗膀胱癌的临床应用提供帮助。方法通过N-N'-羰基二咪唑(CDI)交联剂将治疗膀胱癌的临床药物吡柔比星(pirarubicin,THP)连接在表面氨基化的四氧化三铁(Fe3O4)磁性纳米粒上,制备具有磁性的THP纳米制剂,并在体外考察其磁定位性能和对膀胱癌细胞的抑制作用。结果 THP成功地连接到了粒径40 nm左右的Fe3O4磁性纳米粒上,磁性药物制剂在不同p H值的缓冲液中药物在90%以上,并可在外界磁场作用下定位于靶向部位。对膀胱癌细胞可造成THP和Fe3O4双重抑制效果,抑制率高达58.44%。结论该纳米制剂可通过外界磁场定位于靶向部位,膀胱癌细胞抑制效果明显,为临床定位灌注化疗的应用奠定了基础。     

旋转磁场引导下顺磁纳米铁核素靶向治疗的数学模型

该研究使用MATHCAD软件对旋转磁场引导的顺磁纳米铁核素粒子靶向治疗系统进行理论研究。这个研究是采用一种新的磁性药物-适应于肿瘤治疗的顺磁纳米铁核素（PNINs）,当PNINs被注入血管时,旋转磁场有磁性地引导顺磁纳米铁核素粒子通过循环系统．然后被保留在靶位置。文章探讨建立表征铁磁性药物颗粒在引导磁场中所受磁场力数学模型的方法。首先,由电磁场理论导出的磁场力的一般数学表达式;然后,基于引导磁场磁路的对称性给出其磁场力简化数学模型;最后给出静态磁场和旋转磁场条什下的铁磁性药物颗粒所受磁场力的数学模型。这些数学模型的建立为定性和定量分析铁磁性药物颗粒在引导磁场磁路中的靶向治疗的作用机理奠定了基础。研究结果表明,在靶位置有磁性地靶向聚集顺磁纳米铁核素粒子是可行的和非常有希望的;通过旋转磁场磁导向顺磁纳米铁核素（PNINs）的新方法也是可行的。这个研究显示基于旋转磁场的作用下,PNINs粒子作为一种新的和有效的靶向治疗“药物”具有许多应用前景。     

磁性药物靶向治疗的进展

磁性药物靶向治疗是利用磁场使具有磁响应的药物聚焦在靶部位，提高靶部位药物的浓度，降低药物对正常组织的毒性和副作用。本介绍和评估了磁性药物靶向治疗的发展，并展望了其未来的前景。     

磁性纳米颗粒的产热机制及在肿瘤热疗中的应用

磁热疗是继放射治疗、化学药物治疗后新兴的一种微创肿瘤治疗手段。磁性纳米颗粒在外加磁场下靶向病变部位并积集于此,在交变磁场中磁滞或弛豫产热,使病变部位快速升温。磁热在肿瘤微环境使其发生蛋白质变性、DNA损伤、免疫系统激活等,可在短时间内安全有效地杀死肿瘤细胞。综述磁性纳米颗粒的产热机制,在肿瘤磁热疗中与细胞的相互作用,及与其他肿瘤治疗方式的协同作用,并讨论其对细胞毒性和治疗的副作用。     

磁性药物靶向治疗的进展

磁性药物靶向治疗是利用磁场使具有磁响应的药物聚焦在靶部位,提高靶部位药物的浓度,降低药物对正常组织的毒性和副作用。本文介绍和评估了磁性药物靶向治疗的发展,并展望了其未来的前景。     

磁性液体负载中药定位杀伤癌细胞研究有重要进展

磁性液体负载中药定位杀伤癌细胞研究有重要进展用磁微球载体通过外磁场的导引作用对肿瘤实施定位治疗，可使较小剂量的药物在靶区产生持续较高的药物浓度，提高抗癌药物的选择性，加速并加强疗效，减轻毒副作用，是肿瘤治疗的较好方法。第四军医大学西京医院中医科副主任...     

引导磁场下顺磁纳米铁核素靶向治疗的理论研究

本文提出一种新型的抗肿瘤药物——顺磁纳米铁核素（PNINs）,它具有超顺磁性、放射性活度和较好的磁导向功能的特点,在引导磁场的作用下可有效定位于靶区。根据PNINs的特点与靶向治疗的原理,给出了引导磁场的计算数学模型及计算公式。依据该计算方法进行计算机编程计算,由计算结果绘制出磁场的分布曲线。计算结果表明：在该引导磁场作用下。PNINs能被靶向到靶区,为实现顺磁纳米铁核素靶向治疗肿瘤的临床研究奠定了基础。     

空载磁性壳聚糖微球的靶向性研究

药物磁性微球是由超顺磁性纳米磁粒子、抗癌药物和其它成分共同包埋于高分子聚合物载体中构成,它为抗癌药物的靶向性提供了一种新的途径.本文探讨了空载磁性壳聚糖微球(MCMs)的体内分布.将25只家兔分为A组,靶向组;B组,非靶向组;C组,空白对照组;D组,改变磁场加载时间靶向组;E组,改变磁场距离靶向组.检测各组织中Fe的浓度.结果表明靶向组肺组织中分布百分率高于其它各组,磁场距离的改变对Fe在肺组织中的浓度有很大影响,磁场加载时间对其影响较小.     

磁场对药物的靶向转运

磁场对药物的靶向转运一、引言把化学治疗剂成功地应用于定位疾病治疗的先决条件之一是在生物体中发展药物靶向转运的有效方法。７０年代中叶，引入了药物靶向转运的新概念，其基础是使用外磁场和生物兼容的铁磁颗粒作药物载体［１，２］。８０年代，许多生物医学研究中心...     

An in vitro study of magnetic particle targeting in small blood vessels

The magnetic guidance and capture of particles inside the human body, via the circulatory system, is a novel method for the targeted delivery of drugs. This experimental study confirms in vitro that a dipolar capturing device, based on high-energy magnets with an active space of 8.7 cm x 10 cm x 10 cm, retains colloidal magnetic particles (MPs) (<30 nm) injected in the capillary tubes, where flow velocities are comparable to that encountered in the capillary beds of tumours (<0.5 cm s(-1)). The build-up of the deposition of the MPs was investigated using video imaging techniques that enabled continuous monitoring of the blocking of the vessel whilst simultaneously recording the colloid's flow rate. The parameters of practical importance (length of MP deposit, time of capillary blocking) were estimated and were found to be dependent on the initial fluid velocity, the MP concentration and the distance between the capillary tube and the polar magnetic pieces. Although the tube used in this experiment is larger (diameter = 0.75 mm, length = 100 mm) than that of real capillaries (diameter = 0.01 mm, length approximately 1.5 mm), the flow velocities chosen were similar to those encountered in the capillary beds of tumours and the length/diameter ratio was approximately equal (133 for the present set-up, 100-150 for real capillaries). In these circumstances and using the same magnetic field conditions (intensity, gradient) and MPs, there is close similarity with magnetic capture in a microscopic capillary system. Moreover, the macroscopic system permits analysis of the distribution of MPs in the active magnetic space, and consequently the maximum targetable volume. This study revealed that the capture of particles within the active space was strongly influenced by the gradient of the magnetic field and the flow velocity. Thus, when the magnetic field gradient had medium values (0.1-0.3 T cm(-1)) and the fluid velocity was small (0.15 cm s(-1)), the particles were captured in small, compact and stable deposits (L < 4 cm) and the time necessary for blocking of the capillary was <150 s. Doubling the value for the flow velocity did not influence significantly either the length of MP deposits nor the blocking time. However, lower gradients (<0.1 T cm(-1)) and larger velocities (0.3-0.9 cm s(-1)) result in the formation of larger deposits (4 cm < L < 10 cm) that are unstable at the beginning of the capture process. These large deposits do become stable given sufficient time for the deposition process to take place in conjunction with a decrease in the flow rate. As a consequence, the time necessary for blocking of the capillary increased up to 450 s. Decreasing the MP concentration from 0.02 g cm(-3) to 0.005 g cm(-3) decreased the deposit lengths by approximately 20% and doubled the values of the blocking time. The maximum targetable volume obtained by the present method is approximately 350 cm(3), which corresponds to medium-sized tumours. The capillary vessels were blocked only for the situation that occurs for microcirculation within a tumour. This reduces the concentration of MPs trapped within the normal tissues, which occurs when using particles of micrometre size. This work showed the potential of using colloidal MPs and dipolar magnetic devices for treatment of human patients, when the affected sites are positioned at medium distances from the surface of the body (e.g. head, neck, breast, hands and legs).     

外磁场引导下顺磁纳米铁核素的靶向治疗的理论模型

应用电磁场理论确定引导磁场下顺磁纳米铁核素（PNINs）的运动规律及理论模型。该数学模型及计算机模拟结果成功地解释了铁磁性药物颗粒在引导磁场的作用下随磁场的变化关系，且铁磁性药物颗粒在外引导磁场的作用下能够在靶部位定位分布。理论结果与文献中已发表的实验结果相吻合。     

磁场对微循环的影响

为了探讨磁场对微循环的作用，利用直径０．７ｃｍ、表面磁感强度０．３Ｔ的磁片及磁感强度０．１Ｔ、转速２５００ｒ／ｍｉｎ的旋磁机分别作用于受试者左手无名指３０ｍｉｎ，并记录作用前后微循环改变。结果表明，动、静磁场均可使微血管清晰度、血流速及管径有明显改变，而对管袢数与红细胞聚集没有影响。这一结果提示，微血管扩张、血流速加快是磁场改善微循环的基础。     

The intrinsic shape of the human lumbar spine in the supine, standing and sitting postures: characterization using an active shape model

The shape of the lumbar spine in the sagittal plane varies between individuals and as a result of postural changes but it is not known how the shape in different postures is related. Sagittal images of the lumbar spines of 24 male volunteers were acquired using a positional magnetic resonance scanner. The subjects were imaged lying supine, standing and sitting. An active shape model was used to characterize shape in terms of independent modes of variation. Two modes were identified that described the total (mode 1) and distribution (mode 2) of the curvature. The spinal shape was found to be intercorrelated between the three postures for both modes, suggesting that the lumbar spine has an element of shape that is partially maintained despite postural alterations. Mode 1 values indicated that the spine was straightest when standing and curviest when sitting. Mode 2 values indicated that the distribution in the curvature was most even when sitting and least even when lying supine. Systematic differences in the behaviour of the spine, when changing posture, were found that suggest that the shape of the spine may affect its biomechanics.     

Novel silica-coated iron-carbon composite particles and their targeting effect as a drug carrier

Novel silica-coated iron-carbon composite particles were prepared to be used in the targeting therapy as a drug carrier. The composite particles with diameter of 200-300 nm were obtained successfully via high-energy planetary ball milling and hydrogen reduction processes. The composite particles possess the advantages of activated carbon and magnetic Fe, exhibiting excellent drug adsorption and desorption abilities as well as powerfully magnetic targeting. In in vivo experiment, (99m)TcO(4)-adsorbed composite particles showed prominent biodistribution in the left hepatic lobe of pigs under the control of an external magnetic field. The amount of doxorubicin content of hepatic tissue was 23.8 times higher in targeted area of the left lobe than that in the nontargeted area of the right lobe when doxorubicin-adsorbed composite particles were infused intra-arterially. These results also suggest that the composite particles could penetrate through the capillary wall around tissue interstitium and hepatic cells under the driving of an external magnetic force in targeting area, indicating that the novel silica-coated iron-carbon composite particles could be a potential application in targeted treatment for some kinds of tumor as an effective drug carrier.     

Immunospecific ferromagnetic iron-dextran reagents for the labeling and magnetic separation of cells

Ferromagnetic iron dextran particles were prepared by reacting a mixture of ferrous chloride and ferric chloride with dextran polymers under alkaline conditions. Particles purified by gel filtration chromatography were in the size range of 30–40 nm, had an electron dense core of about 15 nm, were stable against aggregation in physiological buffer, showed little non-specific binding to cells and had a magnetic moment. Protein A from Staphylococcus aureus was covalently coupled to periodate-oxidized ferromagnetic iron-dextran particles. These conjugates were used to indirectly label antigen sites on human red blood cells and thymocytes for visualization by scanning and transmission electron microscopy. Cells labeled with these immunospecific ferromagnetic particles were quantitatively retained by a simple permanent magnet and could be separated from unlabeled cells. Applications of these novel reagents in the separation of cells, cell membranes and receptors and in drug targeting studies are discussed.     

A model for predicting magnetic particle capture in a microfluidic bioseparator

A model is presented for predicting the capture of magnetic micro/nano-particles in a bioseparation microsystem. This bioseparator consists of an array of conductive elements embedded beneath a rectangular microfluidic channel. The magnetic particles are introduced into the microchannel in solution, and are attracted and held by the magnetic force produced by the energized elements. Analytical expressions are obtained for the dominant magnetic and fluidic forces on the particles as they move through the microchannel. These expressions are included in the equations of motion, which are solved numerically to predict particle trajectories and capture time. This model is well-suited for parametric analysis of particle capture taking into account variations in particle size, material properties, applied current, microchannel dimensions, fluid properties, and flow velocity.     

医用磁性纳米粒子非线性磁化谐波信号检测方法研究

医用磁性纳米粒子是一种具有超顺磁性的纳米医学材料,可以通过血液循环聚集于肿瘤组织内部,并利用磁性粒子成像技术令生物体内的磁性粒子浓度可视化,达到肿瘤成像的目的。基于磁性粒子的非线性磁化特性及磁化频率特性,本文提出了磁性粒子信号三次谐波的差分检测方法。通过建模仿真分析,研究交变场下磁性粒子的非线性磁化响应特性以及磁性粒子信号的频谱特性,同时针对各次谐波与医用磁性纳米粒子样品量之间的关系进行研究。在此基础上,搭建信号检测实验系统,分析检测信号的频谱特性及功率谱密度,研究信号与激励频率之间的关系。通过以上方法进行信号检测实验,结果表明:在交变激励场下,医用磁性纳米粒子会产生高于背景场感应信号的尖峰信号,且磁性粒子信号存在于检测信号频谱的奇次项谐波中,频谱能量集中在三次谐波处,可以实现满足医用检测需求的三次谐波磁性粒子信号检测。各次谐波幅值与粒子样品量呈正比关系,可根据其关系确定检测得到的医用磁性纳米粒子样品量。同时,激励频率的选择受到系统灵敏度的限制,在1 kHz的激励频率下达到检测信号三次谐波的检测峰值。本文提出的磁性粒子信号三次谐波的差分检测方法为磁性粒子成像研究中的医用磁性纳米粒子成像信号检测提供了理论及技术支持。     

Detection of pathogenic bacteria by magneto-immunoassays: a review

Magnetic particle-based immunoassays are widely used in microbiology-related assays for both microbial capture, separation, analysis, and detection. Besides facilitating sample operation, the implementation of micro-to-nanometer scale magnetic beads as a solid support potentially shortens the incubation time (for magnetic immuno capture) from several hours to less than an hour. Analytical technologies based on magnetic beads offer a rapid, effective and inexpensive way to separate and concentrate the target analytes prior to detection. Magneto-immuno separation uses magnetic particles coated with specific antibodies to capture target microorganisms, bear the corresponding antigens, and subsequently separate them from the sample matrix in a magnetic field. The method has been proven effective in separating various types of pathogenic bacteria from environmental water samples and in eliminating background interferences. Magnetic particles are often used to capture target cells (pathogenic bacteria) from samples. In most commercially available assays, the actual identification and quantitation of the captured cells is then performed by classical microbiological assays. This review highlights the most sensitive analytic methods (i.e., long-range surface plasmon resonance and electrochemical impedance spectroscopy) to detect magnetically tagged bacteria in conjunction with magnetic actuation.