肿瘤主动靶向磁性纳米粒子研究现状及其在肿瘤热疗中的应用

 磁性纳米粒子已广泛应用于肿瘤的成像和治疗,但限制其临床应用的重大障碍是纳米粒子在肿瘤部位不能达到足够的浓度。主动靶向磁性纳米粒子是磁性纳米粒子表面偶联特定的靶向配体,靶向性结合特定的肿瘤细胞。靶向配体的选择是提高主动靶向性的关键。主动靶向性提高了磁性纳米粒子在肿瘤组织内的浓度,减少对正常组织的毒性,从而使其在肿瘤成像与治疗成为可能。磁感应热疗利用磁介质在外加交变磁场的作用下感应发热,是一种新型的具有前景的肿瘤治疗手段。依靠磁性纳米粒子主动靶向性,磁感应热疗将更好地实现细胞内热疗,提高肿瘤治疗的疗效。     

磁流体靶向热疗对小鼠胰腺癌的作用

 为探讨磁流体靶向热疗对小鼠胰腺癌的体外和动物治疗作用,利用前期建株的小鼠胰腺腺泡细胞癌株(MPC-83)分别进行体外热疗和动物实验.对MPC-83 进行水浴热疗,分别调热疗温度为37、42、46、50℃,作用30 min,显微镜观察细胞形态变化,流式细胞仪检测凋亡和坏死细胞百分比.选择4 周龄雌性昆明种小鼠,建立MPC-83 胰腺癌皮下肿瘤模型,观察磁流体热疗(46℃和50℃)对荷瘤小鼠的作用及其病理学变化.流式细胞仪检测46℃和50℃热疗细胞凋亡和坏死百分比分别为46.13%、89.33%,与对照组比较,差异具有统计学意义(P<0.05).热疗后第14 天,46℃和50℃热疗组肿瘤生长率分别为-0.64±0.73和-0.72±0.79,与3 个对照组比较,肿瘤生长受到明显抑制(P<0.05).病理学检查示磁流体对照组,在注射磁流体24 h 可见散在的磁性纳米微粒在一定范围内分布于肿瘤细胞之间,部分肿瘤细胞和吞噬细胞吞噬了磁性纳米微粒.热疗14 d 肿瘤完全消失的小鼠皮下组织未见肿瘤细胞,可见皮下残存磁性纳米微粒,被吞噬细胞吞噬.各对照组小鼠瘤体生长旺盛,细胞核浓染分裂,可见病理性核分裂像.磁流体靶向热疗可以达到杀伤胰腺癌细胞的理想温度,能有效抑制MPC-83 胰腺癌生长,延长小鼠生存期.     

—株G~-球形趋磁细菌的发现与表征

在玄武湖水域发现一株 Ｇ－ 球形趋磁细菌 Ｘ Ｗ － １ ,光学显微镜下观察,可见菌体在地磁场的作用下,快速北向游移,平均游动速率约为０ ．１４ ｍ ｍ／ｓ ,该菌株对磁场的作用极其敏感．透射电镜观察显示,在每一菌体的细胞壁上镶嵌了１２ 颗左右的磁小体,磁小体的大小和形状均匀一致,每颗磁小体长约６０ｎ ｍ ,宽４０ｎｍ ,ｘ 射线能谱测试分析表明,磁小体为铁的氧化物．     

Enhancement of the efficiency of PEI/liposome transfection by magnetofectins formed via electrostatic self-assembly

One of the major challenges for successful gene therapy is improving the transfection efficiency of non-viral vectors. Magnetic nanoparticles (MNPs) have been developed as enhancers of non-viral vehicles. We prepared MNPs and modified them with polyethyleneimine (PEI), citric acid (CA) or carboxylmethyl-dextran (CMD). Both positively charged MNPs (MNPs@PEI) and negatively charged MNPs (MNPs@CA, MNPs@CMD) could spontaneously form transfection complexes (magnetofectins) with plasmid DNA and PEI/liposome via electrostatic self-assembly. Our results showed as-prepared magnetofectins apparently enhanced PEI/liposome transfection efficiency and/or gene expression level into COS-7 cells with reduced transfection time from 4 h to 15 min under a magnetic field in vitro. Meanwhile, the effect of magnetofection was cell line-dependant. These results suggest that charged MNPs could improve transfection efficiency for non-viral vectors by simply mixing with them and by exerting a magnetic force. Thus such MNPs provide a convenient platform for further applications of gene delivery.     

用于高效磁转染的鱼精蛋白修饰的铁氧磁性纳米粒研究

 功能化铁氧磁性纳米粒在生物医学中应用广泛,可用于肿瘤磁感应热疗、磁共振成像（Magnetic Resonance Imaging,MRI）、药物输送及磁转染等方面。为了探讨鱼精蛋白功能化修饰的铁氧磁性纳米粒的制备及其作为基因载体在体外磁转染中的可行性,采用共沉淀法制备Fe3O4磁性纳米粒,经表面氨基化修饰后在其表面偶联鱼精蛋白。利用透射电镜、傅里叶红外光谱仪、zeta电位与粒度分析仪等,对磁性纳米粒进行形态、粒径及zeta电位分析等表征检测。共聚焦显微镜观察磁转染方法转染报告基因绿色荧光蛋白质粒pEGFP-N1进入HepG2细胞的表达,以真核转染试剂vigofect为对照。结果显示,实验中制备的磁性纳米粒粒径10nm左右,在交变磁场下具有良好的升温性能。鱼精蛋白功能化修饰磁性纳米粒后,其zeta电位进一步增大,更利于与DNA有效结合,在HepG2细胞系,其转染pEGFP-N1质粒的效率高于vigofect。研究表明,鱼精蛋白功能化修饰的铁氧磁性纳米粒可作为磁转染的有效载体,由于其同时具备在交变磁场下升温的性能,在基因治疗联合热疗的研究领域具有一定的应用价值。     

Effect of local hyperthermia induced by nanometer magnetic fluid on the rabbit VX2 liver tumor model

Hyperthermia induced by magnetic nanoparticles is a recent therapeutic approach for local targeting of hyperthermia and thermoablation and is a promising treatment of malignant tumors.The purpose of this study is to evaluate the potential and therapeutic effect of magnetic fluid hyperthermia on the rabbit VX2 liver tumor model.Rabbits bearing liver tumors 14 days after tumor implantation were randomly divided into five groups of 10 cases each,including three control groups and two hyperthermia groups.Hyperthermia was carried out immediately after a single intratumoral injection of uncoated water-based Fe3O4 magnetic fluid under an alternating magnetic field only once as one hyperthermia group and repeated hyperthermia after 5 days as the other treated group.The distribution of magnetic fluid was evaluated by CT scanning.All animals were sacrificed 4 weeks after tumor implantation.The therapeutic effect was determined by tumor size and macroscopic and pathological examination of the liver tumor.The local higher density imaging of intratumoral magnetic fluid deposits compared to the surrounding tissue was clearly observed by CT scanning.Twenty-eight days after tumor implantation,the tumor maximal diameter and tumor volume of two hyperthermia were both significantly less than those of control groups (P＜0.05).Tumor volume inhibition by single or repeated hyperthermia compared to the three control groups was 71.93-79.91% and 92.34-94.46% (P＜0.05),respectively.Under a microscope,coagulation necrosis was observed in the heated area,which had a clear boundary line with the surrounding tissue.The intratumoral distribution of magnetic nanoparticles,especially in the area of necrosis,appeared much more homogenous than in the untreated ones.This study demonstrates that hyperthermia induced by direct intratumoral injection of magnetic fluid can be used safely,and a well-homogenized distribution of high intratumoral temperature without heating adjacent to normal tissue can be achieved.     

In vivo assessment of hepatotoxicity,nephrotoxicity and biodistribution using 3-aminopropyltriethoxysilane-coated magnetic nanoparticles （APTS-MNPs） in ICR mice

The biocompatibility and biodistribution of magnetic nanoparticles （MNPs） in vivo are essential to ensure their safely clinical application. We have studied these aspects with our 3-aminopropyltriethoxysilane-coated magnetic nanoparticles （APTS-MNPs） formulation, which can be used as magnetic induction hyperthermia media. Changes in tissue iron levels were analyzed after intraperitoneal injection of APTS-MNPs to ICR mice. Liver and kidney functions were tested. Heart, liver, spleen, lung, kidney, testis, and brain were sectioned for pathological analysis. Biodistribution of iron in various body tissues changed with time but greater fraction of the injected iron localized in the liver and spleen than in other tissues. Serum showed an increase in AST and LDH fol-lowing APTS-MNPs injection. Histological analyses of selected tissues showed no obvious abnormal changes. In conclusion, APTS-MNPs did not cause continuing changes in the liver and kidney function and thus can be safely used for in vivo application.     

PNA-磁性纳米人工切断试剂定位水解切断DNA

制备了以二氧化硅包裹的磁性纳米粒子（MNPs）为载体，PNA（肽核酸）为识别系统，Ce（Ⅳ）／EDTA配合物为切割系统的PNA-磁性纳米切割试剂．采用TEM对制备的MNPs进行了表征，通过IP—RP—HPLC对切断产物进行了分析．结果表明，该PNA-磁性纳米人工切断试剂可以成功地结合目标DNA，并对其进行定位切断．此外，磁性纳米粒子的引入，使得切断产物的分析更加简单、快捷．     

Anisotropic thermal conductivity of magnetic fluids

Considering the forces acting on the particles and the motion of the particles, this study uses a numerical simulation to investigate the three-dimensional microstructure of the magnetic fluids in the presence of an external magnetic field. A method is proposed for predicting the anisotropic thermal conductivity of magnetic fluids. By introducing an anisotropic structure parameter which characterizes the nonuniform distribution of particles suspended in the magnetic fluids, the traditional Maxwell formula is modified and extended to calculate anisotropic thermal conductivity of the magnetic fluids. The results show that in the presence of an external magnetic field the magnetic nanoparticles form chainlike clusters along the direction of the external magnetic field, which leads to the fact that the thermal conductivity of the magnetic fluid along the chain direction is bigger than that along other directions. The thermal conductivity of the magnetic fluids presents an anisotropic feature. With the increase of the magnetic field strength the chainlike clusters in the magnetic fluid appear to be more obvious, so that the anisotropic feature of heat conduction in the fluids becomes more evident.     

磁性液体奇异的传热特性

磁性液体相比于传统的传热流体来说具有较高的导热性能和传热性能,其流动和传热过程还可以通过磁场控制,因此,磁性液体为强化传热带来了新的机遇,众多研究学者对磁性液体的传热特性进行了研究.通过对近年来有关磁性液体传热特性方面的研究进行整理和分析,总结了磁性液体导热系数和对流传热的实验研究方法,得到了不同的磁性颗粒参数、温度和磁场等因素对磁性液体传热特性的影响;详细阐述了磁性液体在有无磁场下导热系数的研究结果,并对影响导热系数的机理进行了归纳;阐述了磁性液体的对流传热在实验和数值研究方面的进展;指出了磁性液体在传热特性研究方面的进一步工作方向,并对磁性液体在强化传热和传热设备中的应用进行了展望.     

磁流体热疗设备的三维电磁场模拟

为清楚了解磁流体热疗设备产生的电磁场的分布,本文采用有限元方法对自制的设备原型建立三维模型并进行了优化,计算了该模型在静态和谐态下产生的电磁场的分布,对磁极中间的气隙宽度在20～40mm范围内变化时的磁场强度进行了对比．选取气隙宽度为30mm时计算电磁场的磁场强度、电感和涡流损耗,所得结果与实验测量值完全吻合,验证了模拟计算的可靠性．     

In vitro biological effects of magnetic nanoparticles

Magnetic nanoparticles (MNPs) have great potential for a wide use in various biomedical applications due to their unusual properties. It is critical for many applications that the biological effects of nanoparticles are studied in depth. To date, many disparate results can be found in the literature regarding nanoparticle-biological factors interactions. This review highlights recent developments in this field with particular focuses on in vitro MNPs-cell interactions. The effect of MNPs properties on cellular uptake and cytotoxicity evaluation of MNPs were discussed. Some employed methods are also included. Moreover, nanoparticle-cell interactions are mediated by the presence of proteins absorbed from biological fluids on the nanoparticle. Many questions remain on the effect of nanoparticle surface (in addition to nanoparticle size) on protein adsorption. We review papers related to this point too.     

基于有机分子亚铁磁体棱型自旋链外场下的热力学性质研究

基于近来有机高分子亚铁磁体在试验上成功的合成，本文采用量子转移矩阵方法，研究一维反铁磁-铁磁自旋1／2棱型自旋链在外场条件下低温下的热力学性质．磁化强度在低温下随外场的变化出现台阶式的平台结构，并表现出三个临界外场值，反映了系统磁相互耦合作用与热力学波动间的相互竞争；同时磁化率在外场下呈现双峰结构，其来源于系统在外场下的能隙和长程序参量的变化．本文的数值结果表明该棱型链与自旋1-1／2海森堡链性质一致．     

Recent advances in magnetic electrospun nanofibers for cancer theranostics application

Cancer theranostics is a recent concept that aims to combine in the same device diagnostic and therapeutic features. Magnetic nanoparticles (mNPs) are commonly used as a critical part of these systems due to their ability to respond to an external magnetic field. Consequently, mNPs can generate heat when an alternating magnetic field is applied and enhance image contrast in magnetic resonance. However, direct administration of mNPs intravenously or directly in the tumor can lead to undesired side effects because of mNP elimination by macrophages or leakage to healthy tissues. Therefore, mNPs can be retained in a polymeric nanofibrous mesh, thus preventing misplacing or loss of mNPs. Furthermore, these magnetic nanofibers can be directly implanted in the tumor site, thus ensuring high mNPs loading and higher magnetic response. In addition, polymeric nanofibers produced by electrospinning are frequently used to maintain a sustained drug release in the tumor site. Therefore, a magnetic polymeric nanofiber produced by electrospinning is an ideal nanosystem for cancer theranostics application. This review summarizes the most recent developments of magnetic nanofibers produced by electrospinning for cancer theranostics applications.     

磁性纳米颗粒的二维光操纵及团聚效应

我们利用暗场显微镜系统地研究了水剂磁性液体中Fe3O4磁性纳米颗粒在高度聚焦激光作用下的动力学过程.实验研究表明:当激光聚焦在样品池中间时,由于受到沿激光入射方向强散射力和吸收力的作用,磁性纳米颗粒会被排开至光斑的外围;当激光聚焦在样品池上表面时,在光力和样品池上玻片的共同作用下,磁性纳米颗粒会被捕获在样品池的上玻片的下表面并发生团聚效应;此外,我们还研究了不同激光功率作用下形成的磁性纳米团簇对入射白光的透过谱的影响,随着入射激光功率的增加,透过磁性液体的白光的透过率会急剧下降,而且透射谱的中心波长会随着入射激光功率的增加往长波方向移动.     

磁流体的Shliomis体积特性研究

根据Shliomis体积满足的解析关系式,理论分析了磁性颗粒浓度、环境温度和外磁场强度与方位对磁流体的Shliomis体积的影响,并通过数值模拟计算进行了定量的研究.结果表明,磁流体的Shliomis体积随磁性颗粒浓度的增加而增加;随环境温度的增加而减小,在远离磁流体熔点温度时趋于稳定值;随外磁场强度的增加而增加,且与外磁场和磁矩方位夹角有关.纵观各种因素,磁流体的黏度对其Shliomis体积的影响起着关键的作用.研究结果有助于深入了解磁流体中固体磁性颗粒磁矩的弛豫现象.     

水基磁性流体水平加热棒下的池沸腾传热实验研究

研究了磁性微粒浓度、外加磁场对水基磁性流体在水平加热棒加热情况下的沸腾传热影响．实验结果显示，磁性微粒浓度、外加磁场对磁性流体的沸腾换热有很大影响．高浓度的磁粒浓度使磁性流体沸腾换热恶化，对于中低浓度的磁性流体，存在一个最优的磁粒浓度，在该浓度下沸腾传热的强化效果最显，施加磁场时该结论仍然成立．施加磁场使磁性流体的沸腾传热强化．     

Pd催化交叉偶联反应研究进展

综述以Heck反应、Negishi反应和Suzuki反应为主导的Pd催化交叉偶联技术,着重阐述以磁性纳米粒子(MNPs)、高分子为载体的负载型Pd催化剂的研究进展及其在有机化学中的应用.     

The interaction of GSSG modified magnetic nanoparticles with SPC-A1 cells in vitro

Magnetic nanoparticles(MNPs) are promising materials for various biomedical applications,including magnetic resonance imaging,stem cell tracking,gene/drug delivery,and cancer treatment.To increase the effectiveness of MNPs,high capture efficiency and controlled uptake of the particles by cells is required.In this paper we report the cytotoxicity and cellular uptake into SPC-A1 cells of oxidized glutathione(GSSG)-modified MNPs(GSSG@Fe3O4).Experimental findings indicated that GSSG@Fe3O4 were biocompatible,and could be efficiently taken up by SPC-A1 cells(up to 160 pg iron per cell).The internalized GSSG@Fe3O4 was retained in the cell cytoplasm for 6 generations.The uptake of GSSG@Fe3O4 into SPC-A1 cells was energy-,concentration-and time-dependent.Pinocytosis may be involved in the internalization process of GSSG@Fe3O4 into SPC-A1 cells,but this mechanism remains to be elucidated.The controlled and efficient localization of GSSG@Fe3O4 into the cytosol and long intracellular retention provides theoretical and experimental insight into the biomedical applications for these molecules.     

超声乳化法制备纳米Fe3O4磁性颗粒及壳聚糖表面改性

采用超声乳化法制备纳米Fe3O4磁性颗粒,以壳聚糖作为表面活性剂,制备具有生物亲和性的水基Fe3O4磁流体.研究了Fe2+/Fe3+摩尔比、超声时间和表面活性剂用量对磁流体性能的影响.结果表明:当Fe2+/Fe3+摩尔比为1:1·5,滴加氨水时反应温度为70℃时,可制备理想纳米Fe3O4磁性颗粒;超声时间为7·5min左右,质量分数1%的壳聚糖溶液体积占FeO溶液总体积的50%时,有利于壳聚糖分子的包覆,使磁流体具有较高的比饱和磁化强度及稳定性.