综述——新型纳米生物材料的研发：磁性纳米材料：化学合成、功能化与生物医学应用

磁性纳米材料,由于其独特的磁学性能、小尺寸效应,被广泛应用于生物医学领域．本文总结了磁性纳米材料的化学设计与合成、表面功能化方法,及其在核磁共振成像、磁控治疗、磁热疗和生物分离等生物医学领域的应用进展．     

磁场下铁基氧化物纳米材料的生物医学应用

在过去的几年中,磁性纳米材料的快速发展对生物医学变革产生了巨大的影响。作为磁性纳米材料家族重要的一大分类,纳米级铁基氧化物由于其良好的生物相容性、表面易功能化、独特的磁学性质等特点,在生物医学相关领域展现出巨大的应用前景。本综述围绕磁场下铁基氧化物纳米材料的生物医学应用,介绍了近年来其在磁分离、磁性药物靶向(magnetic drug targeting, MDT)、磁共振成像(magnetic resonance imaging, MRI)、磁性粒子成像(magnetic particle imaging, MPI)、磁响应药物释放、磁流体热疗(magnetic fluid hyperthermia, MFH)等领域的研究进展,并对铁基氧化物纳米材料在生物医学领域未来的发展方向进行了展望。     

叶酸修饰的磁性纳米材料在肿瘤诊断和治疗中的应用进展

癌症是威胁人类健康的主要疾病之一,由于检测方法和治疗手段的局限,其成为全球主要的公共卫生难题。叶酸修饰的磁性纳米材料由于同时具有肿瘤细胞靶向性和磁性,不仅可以用于肿瘤组织的成像和肿瘤细胞的检测,还可以用于肿瘤患者的磁热疗、药物载体和基因载体,为肿瘤的靶向诊治提供技术手段。本文综述了叶酸修饰的磁性纳米材料在肿瘤诊断和治疗中的研究进展。     

基于磁性纳米材料的肿瘤靶向治疗研究进展

磁性纳米材料具有独特的磁学性质，可响应外磁场，产生力、热等效应。如在静磁场下将药物磁靶向递送至肿瘤部位；低频交变磁场下可将纳米药物主动渗透至病灶部位，实现瘤内均一分布；中频交变磁场作用下磁滞损耗产生热和增强的活性氧，用于肿瘤治疗。磁性纳米材料同时具有尺寸依赖的磁学性质以及表面多功能化等特点，可将磁靶向、分子靶向以及磁热疗联合。此外，磁性纳米材料具有磁共振成像性能以及纳米酶催化特性，使其在肿瘤诊疗一体化治疗方面获得了广泛应用。近年来，纳米给药系统不断被优化，基于磁性纳米材料的肿瘤靶向治疗也得到了长足的发展。鉴于此，本文围绕提高靶向肿瘤治疗效果，从磁靶向药物治疗、被动靶向磁热疗和主动分子靶向磁热疗、纳米酶特性以及诊疗一体化应用等几方面出发，综述了基于磁性纳米材料的肿瘤靶向治疗研究进展。     

磁性Fe_3O_4/聚苯胺纳米纤维的制备及其固定漆酶研究

合成优良的漆酶固定化载体有利于其进一步应用。通过将磁性纳米颗粒包埋在苯胺的聚合物中形成磁性Fe_3O_4/聚苯胺纳米纤维,作为漆酶固定化载体。透射电镜和红外图谱分别显示了载体的形态结构特征。不同比例的Fe_3O_4与苯胺对载体结构没有明显影响,但会影响酶的负载量。合成载体最大酶负载量为210 mg/g,固定漆酶后的载体导电性能发生变化。固定化漆酶最适pH从4偏移到3.5,在酸性pH范围保持较高的酶活性,最适温度为60℃;在50℃下孵育240 min,能保持约50%的酶活性,于4℃下保存30 d能保持约60%的酶活性;重复使用8次后还能保留70%的酶活性;结果证实了磁性Fe_3O_4/聚苯胺纳米纤维成功合成,对酶有较高的负载量。随着Fe_3O_4的比例增加,载体对漆酶的负载量却减少;漆酶与载体间存在有一定电子交流。固定化漆酶的最适pH向酸性偏移可能和聚苯胺的导电性有关,合成载体显示出良好的热稳定性、储存稳定性和重复使用稳定性,表明磁性Fe_3O_4/聚苯胺纳米纤维是一种优良的酶固定化载体,可以实现酶的高效固定化。     

磁小体的生物合成及用于肿瘤靶向治疗的研究进展

趋磁细菌产生的磁小体是生物膜包被的磁性纳米颗粒,具有优良的纳米磁特性;相比化学合成的磁性纳米材料,其生物来源赋予磁小体更好的生物相容性和遗传可操作性.在生物医学领域,除了用于磁热疗进行肿瘤治疗外,最近几年其作为靶向药物载体、可能参与肿瘤微环境调控的性质得到研究者的广泛关注;同时DNA重组技术的发展解决了磁小体的产率低而趋磁细菌难培养的问题.本文综述了磁小体的生物合成及其相关研究进展,并对其应用前景进行了展望.     

纳米磁颗粒材料在生物医学检测中的研究进展

纳米磁颗粒具有比表面积大、易于修饰、磁响应性强等优良的物理化学特性,经表面修饰后可负载DNA、核酸、蛋白质、细胞等物质,并能在外加磁场的作用下对负载物进行分离、富集、靶向操纵等,可应用于核磁共振成像、磁热疗等技术中,实现分子水平上的医学检测及疾病的诊断治疗。我们简要介绍了近年来纳米磁颗粒在生物医学检测中的研究进展。     

以四甲基氢氧化铵为溶剂的磁性纤维素微球制备、表征及应用

以微晶纤维素和磁性Fe_3O_4纳米粒子为原料,四甲基氢氧化铵溶液为溶剂,通过乳化法制备了磁性纤维素微球。利用扫描电微镜、傅里叶变换红外光谱仪、X线衍射仪、振动样品磁强度计、比表面和孔径分析仪对磁性纤维素微球进行分析表征,结果表明磁性纤维素微球确为纤维素包裹Fe_3O_4纳米粒子形成,且表面粗糙,粒径约200 nm,比表面积13.6 m~2/g,表面微孔体积为0.5 cm~3/g,磁强度为2.0×10~(-3) T/g。磁性纤维素微球染料吸附试验表明,在pH 4～8时其对亚甲基蓝的去除率最大,达到70%以上。     

调制磁性纳米颗粒提高磁热性能的研究

磁性纳米颗粒具有独特的磁学性质,即在外加交变磁场下因产生磁滞释放热量,使其在生物医学领域,特别是肿瘤磁热疗,获得了广泛应用.到目前为止,磁性纳米颗粒介导的磁热疗成为一种治疗癌症的有效手段,已进入临床三期实验.因此,针对磁性纳米颗粒本身,优化设计尺寸、形貌、组分和表面修饰来提高其磁热性能,进而减小临床应用中的颗粒浓度来最小化毒副作用的研究,对肿瘤治疗及生物医药研究具有十分重要的意义.本综述详述如何优化调制磁性纳米颗粒以提高其磁热性能,为高效、低毒的磁性纳米颗粒的设计提供了指导性的研究方向.     

转铁蛋白导向脂质体核磁造影剂纳米粒子(TfNTR-LipNBD-Magnevist)——一种肿瘤靶向磁共振造影剂

造影剂辅助的核磁共振成像是目前肿瘤诊断的最好方法之一.但是由于核磁共振成像内在的低灵敏性以及造影剂的非特异性,导致肿瘤早期诊断较为困难.文章将一种新的肿瘤靶向核磁造影剂纳米粒子应用于早期肿瘤的影像诊断.这种新的肿瘤靶向核磁造影剂纳米粒子由配体转铁蛋白(Tf)、纳米水平的正电脂质体(Lip)载体和临床常用的造影剂Magnevist(TfNIR-LipNBD-Magnevist)三部分构成.另外转铁蛋白和脂质体粒子上,亦标记了荧光物质用于确定转铁蛋白-脂质体-造影剂纳米粒子的靶向性,以及肿瘤的光学影像诊断.在体外实验中,利用激光共聚焦显微镜和光学影像证明了靶向纳米粒子介导的细胞内吞和特异性结合.在裸鼠肿瘤模型中,造影剂纳米粒子TfNIR-LipNBD-Magnevist经尾静脉注入后,显著增强了肿瘤内信号与周围组织的对比度.由造影剂纳米粒子介导的肿瘤内信号显著强于单独Magnevist辅助的肿瘤内信号.同时,利用光学影像方法,在肿瘤内检测到特异的荧光信号.其结果进一步支持了转铁蛋白-脂质体-造影剂(TfNIR-LipNBD-Magnevist)纳米粒子的靶向性和肿瘤影像诊断的有效性.     

普鲁士蓝纳米粒子在生物医学诊断和治疗中的应用及进展

随着生物医学诊断和治疗的持续深入研究,出现了多种医学诊断和治疗新方法,为人类的健康提供了更大的保证,其中纳米生物技术在生物医学诊断和治疗中的应用日益增多,基于纳米技术,开发传统材料的生物医学新应用成为了人们的研究热点。普鲁士蓝是一种历史悠久的蓝色染料,其制备过程简单、绿色、成本低,化学结构稳定,具有优良的物理、化学、光学以及磁性等性能,已经在许多领域得到了广泛的应用。近年来,普鲁士蓝开始在生物医学诊断和治疗领域中崭露头角,它已经成功的被开发为新型的核磁共振造影剂和光声成像造影剂,并且在药物输送系统和光热治疗等领域也开始占有一席之地,开发基于纳米技术的普鲁士蓝的生物医学应用已经成为极具吸引力的研究方向。本文对普鲁士蓝在生物医学诊断和治疗中的应用及进展进行综述。     

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe₃O₄) nanoparticles followed by high-speed emulsification to form a poly(lactic-co-glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering.     

Fe3O4/ 生物可降解复合材料研究

磁性氧化铁纳米粒子因具有尺寸小、低毒性和超顺磁性等特点,已经引起了生物化工、医药工业领域的广泛关注。生物可降解高分子材料是生物医用高分子研究中最活跃的领域之一,已广泛用于外科手术缝合线,植入体材料及药物释放载体等。将Fe3O4和生物可降解高分子材料进行复合,可以扩大两者的应用范围,达到理想的治疗效果,并有望开创临床治疗的新时代。本文介绍了磁性四氧化三铁粒子的化学制备方法,包括共沉淀法、溶胶-凝胶法、微乳液法,并对各种方法的优缺点进行了比较;重点阐述了磁性壳聚糖,磁性聚乳酸,磁性PEG,磁性PCL复合材料的制备,及它们在酶的固定化、磁靶向药物及基因载体等医学领域的应用,显示了Fe3O4/生物可降解复合材料在医学领域的广阔应用前景;最后对复合材料走向临床应用所面临的问题及发展前景进行了讨论。     

Engineered magnetic core shell nanoprobes:Synthesis and applications to cancer imaging and therapeutics

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.     

Magnetic nanoparticles for multi-imaging and drug delivery

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.     

Promising approaches in using magnetic nanoparticles in oncology

The development of new and effective drug delivery systems for cancer treatment represents one of the significant challenges facing biomedical technology in the last decade. Among the different methods of drug delivery, magnetic drug targeting, by enabling specific delivery of chemotherapeutic agents through the use of magnetic nanoparticles and magnetic field gradient, could be a promising approach. Recently, magnetic nanoparticles have attracted additional attention because of their potential as contrast agents for magnetic resonance imaging and heat mediators for cancer therapy. This review summarizes these approaches in the use of magnetic nanoparticles in biomedical applications and novel methods for their optimization.     

Dendrimer functionalized magnetic nanoparticles as a promising platform for localized hyperthermia and magnetic resonance imaging diagnosis

Magnetic iron oxide nanoparticles are a well-explored class of nanomaterials known for their high magnetization and biocompatibility. They have been used in various biomedical applications such as drug delivery, biosensors, hyperthermia, and magnetic resonance imaging (MRI) contrast agent. It is necessary to surface modify the nanoparticles with a biocompatible moiety to prevent their agglomeration and enable them to target to the defined area. Dendrimers have attracted considerable attention due to their small size, monodispersed, well-defined globular shape, and a relative ease incorporation of targeting ligands. In this study, superparamagnetic iron oxide nanoparticles were synthesized via a coprecipitation method. The magnetic nanoparticles (MNPs) had been modified with (3-aminopropyl) triethoxysilane, and then polyamidoamine functionalized MNPs had been synthesized cycling. Various characterization techniques had been used to reveal the morphology, size, and structure of the nanoparticles such as scanning electron microscopy, transmission electron microscope, X-ray diffraction analysis, and vibrating sample magnetometer, Fourier-transform infrared spectroscopy and zeta potential measurements. In addition, the cytotoxicity property of G3–dendrimer functionalized MNPs were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay which confirmed the biocompatibility of the nanocomposites. Dendrimer functionalized MNPs are able to act as contrast agents for MRI and magnetic fluid hyperthermia mediators. A superior heat generation was achieved for the given concentration according to the hyperthermia results. MRI results show that the synthesized nanocomposites are a favorable option for MRI contrast agent. We believe that these dendrimer functionalized MNPs have the potential of integrating therapeutic and diagnostic functions in a single carrier.     

Cancer theranostics: the rise of targeted magnetic nanoparticles

Interest in utilizing magnetic nanoparticles (MNP) for biomedical applications has increased considerably over the past two decades. This excitement has been driven in large part by the success of MNPs as contrast agents in magnetic resonance imaging. The recent investigative trend with respect to cancer has continued down a diagnostic path, but has also turned toward concurrent therapy, giving rise to the distinction of MNPs as potential "theranostics". Here we review both the key technical principles of MNPs and ongoing advancement toward a cancer theranostic MNP. Recent progress in diagnostics, hyperthermia treatments, and drug delivery are all considered. We conclude by identifying current barriers to clinical translation of MNPs and offer considerations for their future development.     

Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.