磁性纳米材料的研究现状及其在神经干细胞移植中的应用

目前 ,常用的磁性纳米材料如三氧化二铁(Fe2 O3)、四氧化三铁 (Fe3O4)、铁钴合金等 ,这些磁性纳米材料具有较好的磁响应性 ,采用适当的方式可以方便地得到纳米磁性材料 ,最小的平均粒度只有纳米 ,粒度一般呈正态分布。磁性纳米材料经过包衣等处理后可作为超顺磁性氧化铁纳米材料用于磁共振成像 ,在疾病诊断上有重要用途。超顺磁性氧化铁粒子 (SPIOs)是具有组织特异性高、更安全的新型的磁共振阴性对比剂 ,目前主要用于富含网状内皮系统的肝、肺、淋巴结、骨髓等增强成像 ,具有其独特的临床诊断价值[2 ] ,但对于网状内皮系统以外的其他组…     

NP-DA-Dextra-FA靶向纳米分子探针对人肝癌细胞的体外磁共振成像研究

目的利用叶酸受体(folate receptor,FR)阳性的Bel7402人肝癌细胞及磁共振成像系统来探讨超顺磁性氧化铁-多巴胺-葡聚糖-叶酸(NP-DA-Dextra-FA)靶向纳米复合物的细胞靶向性并监测其体外成像的可行性。材料与方法研制叶酸靶向纳米分子探针(NP-DA-Dextra-FA)及非靶向纳米分子探针(NP-DADextran)。将人肝癌细胞Bel7402与叶酸靶向纳米分子探针及非靶向探针分别孵育2h后,行普鲁士蓝染色实验及细胞MR成像扫描,分析其T2WI信号强度及信号强度变化率的改变,并行竞争抑制实验。结果不同Fe浓度NP-DA-DextraFA及NP-DA-Dextran纳米分子探针分别与Bel7402细胞孵育后,靶向分子探针组结果显示Bel7402细胞T2信号强度随着铁浓度的升高明显减低,普鲁士蓝染色实验表明大量蓝色铁颗粒沉积位于Bel7402细胞内;非靶向组结果表明Bel7402细胞信号强度减低相对不明显,普鲁士蓝染色示Bel7402细胞内仅见少量蓝色铁颗粒沉积。竞争抑制实验结果表明随着叶酸浓度的升高,T2信号强度逐渐升高。结论叶酸靶向磁性纳米分子探针对人肝癌细胞Bel7402有靶向性,体外磁共振成像可对其靶向性监测。     

超顺磁性(SPIO)氧化铁纳米粒子在肿瘤诊断方面的研究进展

正近年来,随着纳米医学的飞速的发展,分子影像学的不断深化,Fe_3O_4、γ-Fe_2O_3、CO-Fe_2O_4等为主的超顺磁性氧化铁纳米粒在肿瘤诊断方向的研究和应用日益广泛,本文从超顺磁性氧化铁纳米粒子的MRI成像原理出发,以合成方法为基础,阐述近年来超顺磁性氧化铁纳米粒子在肿瘤诊断方面的研究进展,展望超顺磁性纳米粒子未来在肿瘤诊断中     

超顺磁性氧化铁纳米粒子在肝癌诊断与治疗中的研究进展

超顺磁性氧化铁纳米粒子（SPION）作为MR负性对比剂被广泛认知,通过对其进行表面修饰,可明显提高其生物相容性与作用效果。利用外加磁场及交变电流,SPION还可具有靶向传递和磁热疗的作用。本文旨在对SPION在肝癌诊断和治疗方面的研究进展进行综述。     

中等粒径葡聚糖超顺磁性氧化铁纳米颗粒的制备

目的制备中等粒径葡聚糖超顺磁性氧化铁纳米颗粒，评估其作为一种新型的磁共振对比剂可行性。方法采用化学共沉淀法制作葡聚糖超顺磁性氧化铁纳米颗粒，通过凝胶色谱分离葡聚糖超顺磁性氧化铁纳米颗粒，用透射电子显微镜、粒度分析仪、X射线衍射和磁力计对葡聚糖超顺磁性氧化铁纳米颗粒进行表征分析。结果粒度分析仪与电子显微镜检测结果表明，目的粒子均匀一致，葡聚糖超顺磁性氧化铁纳米颗粒核心直径在35—41nm之间，平均粒径40nm。磁力仪检测结果显示，磁化曲线无磁滞现象，表现为超顺磁性，矫顽力为零，饱和磁化强度为23KA／m。结论实验结果表明，所制备的中等粒径聚糖超顺磁性氧化铁纳米可作为一种新型的磁共振造影对比剂，广泛应用于多种疾病的临床诊断和治疗。     

磁性氧化铁纳米粒子造影剂在MRI应用进展

近年来,磁性氧化铁纳米粒子（SPIO）已有广泛的体内应用：如磁共振成像,细胞标记、干细胞祖细胞示踪及组织修复,肿瘤生物探针检测,移植排斥反应的监测等方面,本文综述了USPIO的化学合成、表面修饰以及它们的生物医学应用进展。     

MR对比剂超顺磁性氧化铁脂质体的研究现状:标记特点及其安全性和局限性

背景:近年来超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)对比剂的研发受到了广泛关注,主要体现在干细胞移植后追踪成像、包裹有阿拉伯半乳聚糖的细胞膜受体靶向成像以及SPIO脂质体等剂型的研究方面.目的:对MR对比剂SPIO脂质体的研究现状做一综述.方法:应用计算机检索CNKI和Science Direct数据库中1998-01/2009-09关于超顺磁性氧化铁脂质体的文章,在标题和摘要中以"SPIO,超顺磁性氧化铁,脂质体,MR对比剂"或"SPIO,superparamagnetic iron oxide,Liposome,MR contrastagent"为检索词进行检索.选择文章内容与MR对比剂有关者,同一领域文献则选择近期发表或发表在权威杂志文章.初检得到48篇文献,根据纳入标准选择关于超顺磁性氧化铁脂质体的24篇文献及1部著作进行综述.结果与结论:MR对比剂的不断创新改良对MRI诊断技术的提高起到了不可磨灭的作用.超顺磁性对比剂的代表SPIO在多种疾病的诊断价值上超越了以往的MR对比剂.SPIO脂质体具有更低的毒副作用以及对特异组织良好的靶向性,在实验研究及临床应用上受到广泛关注并被逐步推广.随着功能影像和分子影像的迅速发展,SPIO脂质体在今后应用领域必将更为宽广.     

超小型超顺磁性氧化铁粒子的特性及其在肿瘤MR成像中的应用

超小型超顺磁性氧化铁粒子（ultrasmall superparamag-netic iron oxide，USPIO）是一种新型的MR成像对比剂。因其具血浆半衰期长及易被巨噬细胞吞噬摄取等特点,已有大量研究证实，其在磁共振血管成像（MRA）、组织灌注、网状内皮系统及淋巴结成像等方面有良好的应用前景和潜力。本文就USPIO在肿瘤MR成像方面的应用研究作一综述。     

超顺磁性纳米颗粒治疗肿瘤的应用进展

背景,近年来纳米颗粒在肿瘤热疗、基因载体研究、靶向药物治疗等方面得到迅速发展,特别是纳米颗粒载药系统已成为肿瘤治疗的又一突破口.目的:对超顺磁性纳米颗粒在医学领域特别是肿瘤治疗方面的应用及其机制进行概述.方法:应用计算机检索Medline数据库(2000-01/2009-10),以"Superparamagnetic,Nanoparticles,Targeting"为检索词;应用计算机检索中国期刊网(CNKI)(2005-01/2009-10),万方数据库(2005-01/2009-10),以"磁性、纳米颗粒、靶向"为检索词.结果与结论:共收集123篇关于磁性纳米颗粒靶向作用的文献,中文24篇,英文108篇.排除发表时间较早、重复及类似研究,纳入30篇符合标准的文献.超顺磁性纳米颗粒是指具有磁响应性的纳米级粒子,其直径一般小于30 nm,当磁性纳米粒子的粒径小于其超顺磁性临界尺寸时,粒子进入超磁性状态.超顺磁性纳米颗粒除了通过血液循环进入炎症肿瘤相关部位外,还可被广泛存在于肝脏、脾脏、淋巴结的网状细胞-内皮吞噬系统(reticulo-eneothelial system,RES)的细胞所识别.研究发现经过表面修饰的载药纳米颗粒,可跨血脑屏障转运,其机制可能与血脑屏障的连接结构--毛细血管,其内皮细胞通过低密度脂蛋白介导的胞吞作用有关.目前合成生物相容性磁性纳米颗粒的方法有很多,但最常用的合成生物相容Fe3O4磁性纳米颗粒的方法为共沉淀法.超顺磁性纳米颗粒在外加磁场的作用下可具有靶向性,且四氧化三铁的晶体对细胞无毒,其作为基因载体及药物载体被广泛应用于医学研究,为肿瘤的治疗开辟了新的途径.但对于外置磁场,如何全面的避开内皮吞噬系统的吞噬,防止治疗过程中药物性血栓的生成等尚存在不足.     

靶向超顺磁性脂质体整合素受体MR成像实验研究

目的：合成靶向性超顺磁性长循环脂质体,进行肿瘤特异性磁共振成像。方法：将RGD短肽连接在包封SPIO的长循环脂质体表面,合成靶向性和非靶向长循环脂质体。与HUVEC细胞孵育流式细胞分析确定其受体亲和力;建立兔荷VX2肿瘤模型并进行磁共振靶向成像研究,观察其强化特征并与肿瘤标本的组织学检查相对照。结果：靶向超顺磁性脂质体对αvβ3整合素受体具有较高的特异性亲和力,与非靶向造影剂比较有显著统计学差异（P<0.002）;该靶向造影剂能够在肿瘤内缓慢浓聚,给药后15h达最大值,此时对比噪声比（CNR）降至最低（P<0.01）。非靶向造影剂给药后2h即达最大浓聚,此时CNR最低（P<0.05）。两者强化机制不同。结论：RGD－超顺磁性长循环脂质体具有较高的弛豫率,能与αvβ3整合素受体特异性结合,在肿瘤特异性浓聚,并能够用MRI扫描进行证实。     

Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

Purpose  

In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications.     

The Use of Superparamagnetic Iron Oxide Nanoparticles to Assess Cardiac Inflammation

Superparamagnetic iron oxide-based contrast agents enhance and complement in vivo magnetic resonance imaging (MRI) by shortening T2 and T2* relaxation times. They are able to highlight areas of cellular inflammation, being detected and engulfed by cells of the reticuloendothelial system, and can be targeted to specific cellular processes or subtypes using antibody or ligand labeling. These agents have been used preclinically for the assessment of cardiac transplant rejection, cardiomyocyte apoptosis, myocardial infarction, myocarditis, and stem and endothelial cell imaging, with clinical applications now emerging. We here review recent studies using iron oxide particles to image cardiac inflammation, and highlight the potential of these agents for future clinical and research applications.     

超顺磁性氧化铁纳米颗粒体外标记兔骨髓间充质干细胞的安全性以及MRI成像特征

背景：传统的干细胞标记方法常需要病理组织学等侵袭性手段检测,无法动态观察整个实验过程,也不适合临床研究。目的：观察超顺磁性氧化铁纳米颗粒体外标记对兔骨髓间充质干细胞生物学特性的影响以及标记兔骨髓间充质干细胞的体外MRI成像特征。方法：采用红细胞裂解贴壁法培养扩增兔骨髓间充质干细胞。采用不同浓度超顺磁性氧化铁纳米颗粒（100,50,25,12.5mg/L）联合多聚赖氨酸（0.75mg/L）标记兔骨髓间充质干细胞。对标记兔骨髓间充质干细胞进行MRI检测,观察其成像特征。结果与结论：25mg/L的超顺磁性氧化铁纳米颗粒联合0.75mg/L多聚赖氨酸标记兔骨髓间充质干细胞具有较好的安全性和有效性。此浓度对细胞的生长活性没有影响,不影响骨髓间充质干细胞的成骨成脂分化能力。MRI扫描在T2^＊WI序列上能明显有效地显像超顺磁性氧化铁纳米颗粒标记的兔骨髓间充质干细胞。     

Molecular imaging in cardiovascular magnetic resonance imaging: current perspective and future potential

The development of novel imaging agents and techniques is allowing some biological events to be imaged in vivo with magnetic resonance imaging (MRI) at the cellular and subcellular level. In this paper, the use of novel gadolinium chelates and superparamagnetic iron oxide nanoparticles for molecular MRI of the cardiovascular system is extensively reviewed. The physical properties of these imaging agents and the pulse sequences best suited to their visualization are extensively discussed. The application of molecular MRI in diseases of the vasculature and myocardium is then reviewed. The clinical experience to date, as well as the promise and potential impact of molecular MRI, is extensively discussed.     

Co‐precipitation of DEAE‐dextran coated SPIONs: how synthesis conditions affect particle properties,stem cell labelling and MR contrast

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co‐precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co‐precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T₂ and T₂^* relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co‐precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd.     

Can we accurately quantify nanoparticle associated proteins when constructing high‐affinity MRI molecular imaging probes?

Targeted magnetic resonance contrast agents (e.g. iron oxide nanoparticles) have the potential to become highly selective imaging tools. In this context, quantification of the coupled amount of protein is essential for the design of antibody‐ or antibody fragment‐conjugated nanoparticles. Nevertheless, the presence of magnetic iron oxide nanoparticles is still an unsolved problem for this task. The aim of the present work was to clarify whether proteins can be reliably quantified directly in the presence of magnetic iron oxide nanoparticles without the use of fluorescence or radioactivity. Protein quantification via Bradford was not influenced by the presence of magnetic iron oxide nanoparticles (0–17.2 mmol Fe l^?1). Instead, bicinchoninic acid based assay was, indeed, distinctly affected by the presence of nanoparticle‐iron in suspension (0.1–17.2 mmol Fe l^?1), although the influence was linear. This observation allowed for adequate mathematical corrections with known iron content of a given nanoparticle. The applicability of our approach was demonstrated by the determination of bovine serum albumin (BSA) content coupled to dextrane‐coated magnetic nanoparticles, which was found with the QuantiPro Bicinchoninic acid assay to be of 1.5 ± 0.2 µg BSA per 1 mg nanoparticle. Both Bradford and bicinchoninic acid assay protein assays allow for direct quantification of proteins in the presence of iron oxide containing magnetic nanoparticles, without the need for the introduction of radioactivity or fluorescence modules. Thus in future it should be possible to make more precise estimations about the coupled protein amount in high‐affinity targeted MRI probes for the identification of specific molecules in living organisms, an aspect which is lacking in corresponding works published so far. Additionally, the present protein coupling procedures can be drastically improved by our proposed protein quantification method. Copyright © 2011 John Wiley & Sons, Ltd.     

Magnetomotive Ultrasound Imaging Systems: Basic Principles and First Applications

This review discusses magnetomotive ultrasound, which is an emerging technique that uses superparamagnetic iron oxide nanoparticles as a contrast agent. The key advantage of using nanoparticle-based contrast agents is their ability to reach extravascular targets, whereas commercial contrast agents for ultrasound comprise microbubbles confined to the blood stream. This also extends possibilities for molecular imaging, where the contrast agent is labeled with specific targeting molecules (e.g., antibodies) so that pathologic tissue may be visualized directly. The principle of action is that an external time-varying magnetic field acts to displace the nanoparticles lodged in tissue and thereby their immediate surrounding. This movement is then detected with ultrasound using frequency- or time-domain analysis of echo data. As a contrast agent already approved for magnetic resonance imaging (MRI) by the US Food and Drug Administration, there is a shorter path to clinical translation, although safety studies of magnetomotion are necessary, especially if particle design is altered to affect biodistribution or signal strength. The external modulated magnetic field may be generated by electromagnets, permanent magnets, or a combination of the two. The induced nanoparticle motion may also reveal mechanical material properties of tissue, healthy or diseased, one of several interesting potential future aspects of the technique.     

Single‐cell detection by gradient echo 9.4 T MRI: a parametric study

Recent studies have shown that cell migration can be monitored in vivo by magnetic resonance imaging after intracellular contrast agent incorporation. This is due to the dephasing effect on proton magnetization of the local magnetic field created by a labelled cell. Anionic iron oxide nanoparticles (AMNP) are among the most efficient and non‐toxic contrast agents to be spontaneously taken up by a wide variety of cells. Here we measured the iron load and magnetization of HeLa tumour cells labelled with AMNP, as a function of the external magnetic field. High‐resolution gradient echo 9.4 T MRI detected individual labelled cells, whereas spin echo sequences were poorly sensitive. We then conducted a systematic study in order to determine the gradient echo sequence parameters (echo time, cell magnetization and resolution) most suitable for in vivo identification of single cells. Copyright © 2006 John Wiley & Sons, Ltd.     

Two-Step <Emphasis Type="Italic">In Vivo</Emphasis> Tumor Targeting by Biotin-Conjugated Antibodies and Superparamagnetic Nanoparticles Assessed by Magnetic Resonance Imaging at 1.5 T

Purpose  

The purpose of this study was to assess two-step in vivo tumor targeting by specific biotin-conjugated antibodies and ultrasmall superparamagnetic iron oxide (USPIO)-anti-biotin nanoparticles as contrast agents for magnetic resonance imaging (MRI) at 1.5 T.     

Imaging of Her2‐targeted magnetic nanoparticles for breast cancer detection: comparison of SQUID‐detected magnetic relaxometry and MRI

Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, noninvasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single‐core iron oxide nanoparticles by superconducting quantum interference device (SQUID)‐detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2‐expressing MCF7/Her2‐18 (breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle‐labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125 000 nanoparticle‐labeled cells at 3 cm from the SQUID sensors. T₂‐weighted MRI yielded a detection limit of 15 600 cells in a 150 µl volume, with r₁ = 1.1 mm ^?1 s^?1 and r₂ = 166 mm ^?1 s^?1. Her2‐targeted nanoparticles were directly injected into xenograft MCF7/Her2‐18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co‐registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID‐detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle‐based therapies. Copyright © 2012 John Wiley & Sons, Ltd.