介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

有机/无机杂化的介孔有机硅纳米颗粒因其高的比表面积、丰富的介孔孔道、功能性的骨架以及高的药物装载量等特点而在生物医学领域受到广泛关注。本研究提出以二硫键桥接的有机/无机杂化介孔有机硅纳米颗粒为载体共装载化疗药物和光热剂, 设计制备以DNA分子作为控释“开关”修饰介孔有机硅纳米颗粒的纳米递送系统(ICG/DOX-MONs @DNA₂₀)。该纳米递送系统结合了光热剂的光热效应以及DNA分子随温度升高而从颗粒表面脱附的特性, 可实现近红外光照射激发药物在肿瘤细胞中的控制释放, 同时获得药物化疗-光热联合治疗肿瘤的效果。实验结果表明, 纳米递送系统在近红外光照下能迅速升温至43 ℃以上的热疗温度, 而且在37 ℃条件下6 h内仅缓慢释放药物12.3%, 而当温度升至43 ℃时则快速释放药物52.4%; 细胞实验显示该纳米递送系统能够被HeLa肿瘤细胞吞噬, 在近红外光照下有明显的药物化疗-光热联合治疗效果。因此, ICG/DOX-MONs@DNA₂₀纳米递送系统在药物化疗-光热联合治疗肿瘤方面具有应用前景。     

氧化铁纳米颗粒示踪干细胞的临床转化研究进展

氧化铁纳米颗粒由纳米结构的氧化铁分子和表面包被的有机或无机涂层组成,具有独特的磁性和优异的生物相容性,在医学领域中应用非常广泛。当氧化铁纳米颗粒核心的氧化铁直径小于10～15 nm时,在一定温度范围内表现出超顺磁性,常用于磁共振成像,并且已经有多种基于超顺磁性氧化铁纳米颗粒的相关产品批准用于临床。在人体,移植干细胞在体内的迁移、分布和归巢仍然没有有效的示踪方法,严重制约着研究人员了解干细胞治疗机理及评价治疗效果,而超顺磁性氧化铁纳米颗粒与磁共振成像技术的结合为干细胞示踪的临床转化带来了希望,并将有望成为干细胞示踪的"金标准",但是目前还未有任何纳米铁剂批准用于临床干细胞标记和体内示踪。综述了纳米铁颗粒在干细胞示踪方面的临床转化研究现状,以及面临的机遇和挑战,并展望了今后的发展方向与前景。     

磁性氧化铁高效磁共振造影剂的制备及应用

采用高温热分解法, 以乙酰丙酮铁为铁源, 生物相容性良好的聚乙二醇(PEG1000)作为溶剂、还原剂及修饰剂制备PEG修饰的氧化铁纳米粒子(PEG-SPIONs), 并研究其在小鼠体内的造影效果。X射线衍射(XRD)分析表明样品中含有Fe₃O₄晶相。透射电镜(TEM)结果显示, 合成的PEG-SPIONs形貌均一, 主要为等轴晶形, 纳米粒度及电位分析表明其表面呈负电性, 分散在水中的动力学粒径为20 nm。磁性能结果表明合成的PEG-SPIONs室温下具有超顺磁性, 并且具有较高的r₂/r₁值。细胞活性研究表明PEG-SPIONs具有较低的生物毒性, 体内的磁共振成像结果显示出PEG-SPIONs优异的对比增强效果, 说明PEG-SPIONs可以作为高效的T₂磁共振成像造影剂。     

超顺磁性磷酸钙复合支架的制备及性能研究

采用共混-真空烧结方法制备了一系列超顺磁性磷酸钙复合支架, 通过SEM、EDS、XRD和VSM等手段对所制备的材料性能进行表征, 并考察了其在水中的稳定性以及Ros17/2.8细胞在材料表面的黏附生长情况。结果表明: 该方法所制备的超顺磁性复合支架具有多级连通孔结构, 磁性纳米颗粒在基体中分布均匀, 结合牢固且复合量精确可控, 在水中具有良好的稳定性。真空烧结避免了磁性纳米颗粒在烧结过程中发生氧化和相变, 使复合支架继续保持超顺磁性并具有良好的磁性能, 且该磁性支架有利于细胞的黏附和生长, 具有较好的生物相容性, 在组织工程中有潜在的应用前景。     

γ-Fe2O3超顺磁纳米颗粒/壳聚糖复合胶体的制备、表征及其对Pb(Ⅱ)的吸附研究

超顺磁纳米材料因其具有较好的吸附性能、良好的生物相容性和易固液分离等优点而在重金属的去除研究中备受关注。将壳聚糖与由共沉淀法制备的γ-Fe₂O₃超顺磁纳米颗粒复合制备γ-Fe₂O₃超顺磁纳米颗粒/壳聚糖复合胶体体系,利用动态光散射与小角X射线散射技术对胶体粒径及结构进行原位表征,并考察该胶体体系对Pb(Ⅱ)的吸附性能。结果表明:γ-Fe₂O₃超顺磁纳米颗粒多分散系数较小,与壳聚糖复合后呈软团聚的胶体结构;该胶体体系对Pb(Ⅱ)的吸附动力学符合准二级吸附动力学模型,动力学拟合最大吸附容量为42.9 mg/g,说明该胶体体系对Pb(Ⅱ)具有优异的吸附性能且以化学吸附为主。该胶体体系可为Pb(Ⅱ)污染的水体治理提供实验和技术参考。     

Fe2O3纳米纤维锂离子电池负极材料的制备及其电化学性能研究

Fe₂O₃具有理论比容量高和价格低廉等特点, 已成为锂离子电池负极材料的研究热点之一。实验以不同质量比PVP/FeCl₃溶液为前驱体, 静电纺丝技术制备PVP/FeCl₃纳米纤维并热处理, 得到不同直径的Fe₂O₃纳米纤维负极材料, 并以水热合成法制备了Fe₂O₃纳米颗粒。利用X射线衍射、热重、红外光谱、扫描电镜、透射电镜和恒流充放电等测试手段对材料的物相、微观形貌和电化学性能进行表征。结果表明, Fe₂O₃纳米纤维比Fe₂O₃纳米颗粒表现出更优的电化学性能, 直径为160 nm的Fe₂O₃纳米纤维负极材料的倍率性能和循环性能最佳, 材料在0.1 A/g电流密度下的可逆容量为827.3 mAh/g;在2 A/g电流密度下70次循环放电比容量有439.1 mAh/g。     

月桂酸/十四醇纳米复合相变材料的制备及性能研究

选择月桂酸(LA)-十四醇(TD)复合相变材料作为基材,分别以Al_2O_3、Fe_2O_3和CuO纳米颗粒作为添加剂,SDBS为分散剂,制备了LA-TD纳米复合相变材料。从分散剂添加量、超声分散时间、纳米颗粒添加种类和质量分数方面研究了Al_2O_3、Fe_2O_3和CuO 3种纳米复合相变材料的最佳制备条件。在最佳制备条件下,利用导热系数测定仪和DSC测试确定了3种纳米复合相变材料的导热系数、相变温度及相变潜热,并对复合相变材料进行了降温步冷和升温融化实验,研究了纳米颗粒对复合相变材料吸/放热速率的影响。最终确认Fe_2O_3纳米颗粒对LA-TD复合相变材料的传热强化效果最好,1%Fe_2O_3含量的LA-TD纳米复合相变材料的导热系数为0.3319 W/(m·K),较LA-TD纯相变材料提高了36.88%,其相变温度和相变潜热分别为24.76℃和112.61 J/g。纳米颗粒的添加提高了复合相变材料的放热速率,从50～15℃的凝固时间较LA-TD纯相变材料缩短了260 s(7.22%),但纳米颗粒的添加增加了流体粘度,不利于相变融化过程的自然对流。300次的融化/凝固热循环实验表明LA-TD/Fe_2O_3纳米复合材料具有良好的热稳定性。     

一种新型球状纳米氧化铁的制备

以Fe(NO₃)₃·9H₂O为原料、以尿素为沉淀剂,用热解前驱体法制备出直径为40~60 nm的球状纳米氧化铁。使用XRD、SEM和EDS等手段对其表征,研究了Fe³⁺浓度、反应温度等因素对纳米氧化铁的粒径和形貌的影响、确定了球状纳米氧化铁的制备条件并分析了球状纳米氧化铁的形成机理。结果表明：随着Fe(NO₃)₃·9H₂O溶液温度的提高纳米氧化铁的结晶度随之提高、粒径增大。Fe(NO₃)₃·9H₂O的浓度对纳米氧化铁样品的粒度和形貌的影响不大。球状氧化铁纳米的形成机理是：铁源在水热条件下水解和结晶生成棕黄色絮状沉淀FeOOH,FeOOH在高温高压条件下溶解和再结晶生成了球状纳米氧化铁。     

二肉豆蔻酰磷脂酰胆碱修饰的氧化铁纳米粒子在PC-12细胞内的分布

有机物包覆的超顺磁性氧化铁纳米粒子(Superparamagnetic iron oxide nanoparticles,SPIONs)因具有良好的水溶性和生物相容性而被越来越多地用作生物医学研究的工具。采用简便的高温热分解法合成聚乙二醇(Polyethylene glycol,PEG)和聚乙烯亚胺(Polyethyleneimine,PEI)修饰的超顺磁性氧化铁纳米粒子(PEG/PEI-SPIONs),再在其表面通过氢键相互作用接枝二肉豆蔻酰磷脂酰胆碱(1, 2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC),成功制备了DMPC-SPIONs。由热重结果分析可知DMPC的接枝率约为31.7%(质量分数)。将PEG/PEI-SPIONs和DMPC-SPIONs分别与PC-12细胞孵化,对孵化后的细胞进行表征和分析发现,大量的DMPC-SPIONs进入了细胞,而PEG/PEI-SPIONs进入细胞内的量较少。这表明DMPC对于氧化铁纳米粒子进入细胞起到关键作用。通过透射电镜观察与DMPC-SPIONs孵化的PC-12细胞发现,氧化铁纳米粒子密集分布于溶酶体、线粒体、内质网和细胞核膜表面,另外,也有一部分DMPC-SPIONs分布在细胞膜上的纤毛附近,并观察到细胞膜对纳米粒子的内吞现象。DMPC-SPIONs良好的膜透过性及在胞内细胞器的密集分布使其在磁热疗、磁共振成像、药物输运等生物医学领域具有广阔的应用前景。     

蒙脱土/ 二氧化钛/ 聚酰亚胺纳米杂化薄膜低温力学及热稳定性能研究

利用插层法和溶胶-凝胶法制备了不同含量的蒙脱土/ 二氧化钛/ 聚酰亚胺(MMT/ TiO₂ / PI) 纳米杂化薄膜。采用傅立叶红外光谱、紫外可见光谱、扫描电镜和热重分析等对该体系的分子结构、断口形貌和热性能进行了表征, 同时研究了聚酰亚胺杂化薄膜低温(77 K) 力学性能。结果表明, 纳米粒子与基体结合情况良好, 热分解温度Td有所上升。TiO₂ / PI 杂化薄膜低温拉伸强度随TiO₂ 质量分数增加而有所下降; 而MMT/ TiO₂ / PI 杂化薄膜拉伸强度随TiO₂质量分数增加而增加并在TiO₂质量分数为2 %时达到最大值, 说明TiO₂ 与MMT 超混杂产生了协同效应。另外, 弹性模量随无机颗粒含量的增加而提高, 但断裂伸长率则下降。      

Antioxidant efficacy of chitosan/graphene functionalized superparamagnetic iron oxide nanoparticles

The antioxidant potential of superparamagnetic iron oxide nanoparticles functionalized with chitosan and graphene were examined in the present work. Coprecipitation technique was followed for the synthesis of iron oxide nanoparticles. Graphene-iron oxide nanocomposites were synthesized by mechanical mixing followed by the heat treatment at moderate temperature. The chitosan coated iron oxide nanoparticles were prepared by dispersing nanoparticles in chitosan solution. The nanoparticles/nanocomposites were characterized using XRD, SEM, TEM and HAADF-STEM for phase structure, morphology and elemental analysis. The superparamagnetic behavior of nanoparticles/nanocomposites were confirmed by magnetic measurements using vibrating sample magnetometry. Antioxidant efficacy of these nanoparticles/nanocomposites were investigated in terms of free radical scavenging and reducing potential using an array of in vitro assay system. Ferric reducing antioxidant power (FRAP) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) were used for the antioxidant capacity. The investigation suggests that the graphene improves the antiradical response of iron oxide nanoparticles at higher concentration which is almost comparable to the ascorbic acid used as standard.     

Effect of Synthesis Parameters on the Properties of Superparamagnetic Iron Oxide Nanoparticles

Iron oxide nanoparticles were coprecipitated in air medium using different sodium hydroxide (NaOH) concentrations, and their structural and magnetic properties were studied. It was observed that the precipitation of superparamagnetic iron oxide nanoparticles could be achieved above a critical NaOH concentration. This was followed by the investigation of the effect of the stirring rate on the structural and magnetic properties of the nanoparticles precipitated at 8.5?M NaOH and over. Morphological observation made by a transmission electron microscope (TEM) showed that the particle size of iron oxide nanoparticles was around 7.5?nm. Magnetization curves measured by a vibrating sample magnetometer showed zero coercivity indicating that the samples are superparamagnetic and the highest saturation magnetization (70.4?emu/g) was obtained at the stirring rate of 1100?rpm. The mean particle sizes of iron oxide nanoparticles calculated from the magnetization data are found to be consistent with the particle sizes obtained from the TEM images.     

Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics

Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. Membrane‐bound 70 kDa heat shock protein (mHsp70) is ubiquitously expressed on the cell membrane of various tumor types but not normal cells and therefore provides a tumor‐specific target. The serine protease granzyme B (GrB) that is produced as an effector molecule by activated T and NK cells has been shown to specifically target mHsp70 on tumor cells. Following binding to Hsp70, GrB is rapidly internalized into tumor cells. Herein, it is demonstrated that GrB functionalized SPIONs act as a contrast enhancement agent for magnetic resonance imaging and induce specific tumor cell apoptosis. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting are found to further enhance the therapeutic efficacy of GrB‐SPIONs in different tumor mouse models.     

LHRH-functionalized superparamagnetic iron oxide nanoparticles for breast cancer targeting and contrast enhancement in MRI

This paper shows that superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH–SPIONs), can be used to target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging of breast cancer xenografts. A combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used in our experiments, to investigate the specific accumulation of the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) in cancer cells. The contrast enhancement of conventional T2 images obtained from the tumor tissue and of breast cancer xenograft bearing mice is shown to be much greater than that in saline controls, when the tissues were injected with LHRH–SPIONs. Magnetic anisotropy multi-CRAZED images of tissues extracted from mice injected with SPIONs were also found to have enhanced MRI contrast in breast cancer xenografts and metastases in the lungs.     

Ascorbic acid-mediated synthesis and characterisation of iron oxide/gold core–shell nanoparticles.

The current article reports on providing surface modification of magnetic nanoparticles with gold to provide stability against aggregation. Gold-coated magnetite nanoparticles were synthesised to combine both magnetic as well as surface plasma resonance (SPR) properties in a single moiety. The nanocomposites were produced by reduction (using ascorbic acid) of gold chloride on to the surface of iron oxide nanoparticles. Ascorbic acid not only acts as a reducing agent, but also the oxidised form of ascorbic acid i.e. Dehydro-ascorbic acid acts as a capping agent to impart stability to as synthesised gold-coated iron oxide nanocomposites. The synthesised nanocomposite was monodispersed with a mean particle size of around 16 nm and polydispersity index of 0.190. X-ray diffraction analysis confirms presence of gold on the surface of magnetite nanoparticles. The synthesised nanocomposites had a total organic content of around 3.2% w/w and also showed a shifted SPR peak at 546 nm as compared to gold nanoparticles (528 nm). Both uncoated and gold-coated magnetite exhibited superparamagnetic behaviour at room temperature. Upon coating with gold shell, saturation magnetisation of iron oxide nanoparticles decreases from 42.806 to 3.54 emu/gram.     

Synthesis,self-assembly,and characterization of PEG-coated iron oxide nanoparticles as potential MRI contrast agent

Aim: Investigated the self-assembly and characterization of novel antifouling polyethylene glycol (PEG)-coated iron oxide nanoparticles as nanoprobes for magnetic resonance imaging (MRI) contrast agent. Method: Monodisperse oleic acid-coated superparamagnetic iron oxide cores are synthesized by thermal decomposition of iron oleate. The self-assembly behavior between iron oxide cores and PEG-lipid conjugates in water and their characteristics are confirmed by transmission electron microscope, X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometer. Result: Dynamic light scattering shows superparamagnetic iron oxide nanoparticles coated with PEG are stable in water for pH of 3–10 and ionic strengths up to 0.3 M NaCl, and are protein resistant in physiological conditions. Additionally, in vitro MRI study demonstrates the efficient magnetic resonance imaging contrast characteristics of the iron oxide nanoparticles. Conclusion: The result indicates that the novel antifouling PEG-coated superparamagnetic iron oxide nanoparticles could potentially be used in a wide range of applications such as biotechnology, MRI, and magnetic fluid hyperthermia.     

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging (MRI) contrast agents or in drug delivery applications. In this study, a novel approach to prepare magnetic polymeric nanoparticles with magnetic core and polymeric shell using inverse microemulsion polymerization process is reported. Poly(ethyleneglycol) (PEG)-modified superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared inside the aqueous cores of AOT/n-Hexane reverse micelles and characterized by various physicochemical means such as transmission electron microscopy (TEM), infrared spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM), and ultraviolet/visible spectroscopy. The inverse microemulsion polymerization of a polymerizable derivative of PEG and a cross-linking agent resulted in a stable hydrophilic polymeric shell of the nanoparticles. The results taken together from TEM and AFM studies showed that the particles are spherical in shape with core-shell structure. The average size of the PEG-modified nanoparticles was found to be around 40-50 nm with narrow size distribution. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles with saturation magnetization values between 45-50 electromagnetic units per gram. The cytotoxicity profile of the nanoparticles on human dermal fibroblasts as measured by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the particles are nontoxic and may be useful for various in vivo and in vitro biomedical applications.     

雾化-热分解法合成氧化铁纳米粒子及其磁性能

建立了将五羰基铁超声雾化、分段加热分解-氧化及产物收集-修饰一体化的氧化铁纳米粒子合成装置,研究了不同温度参数对纳米粒子的相组成和形貌的影响,并通过在雾化液及收集液中添加修饰剂以控制合成纳米粒子的粒径和分散性。采用XRD、TEM和SQUID对合成的纳米粒子进行了表征。成功合成了不同结晶性和分散性的球形γ-Fe2O3纳米粒子。随着粒径减小,合成纳米粒子由顺磁性过渡到超顺磁性。     

Characterizations of Iron Particles Reduced from Iron Oxide Nanoparticles Under Hydrogen Atmosphere

Submicron iron particles were obtained by the reduction of co-precipitated superparamagnetic iron oxide nanoparticles under hydrogen atmosphere. The reduction was carried out at the temperatures ranging from 200 to 1000 °C. The magnetic properties were investigated in accordance with the structural properties. According to the X-ray diffraction patterns, the increase of crystallization was followed by the conversion from iron oxide to iron and also the particle size increased as the reduction temperature increased. Morphology observed by transmission electron microscope showed that the particles were individually seen at low temperatures; however, they stacked together and became larger at high temperatures. Magnetic measurements with a vibrating sample magnetometer disclosed that the saturation magnetization steadily increased with increasing temperature and almost stabilized at 800 °C. Highest saturation magnetization obtained by the reduction process is ～211 emu/g, which is close to that of bulk iron. It is disclosed that, at all temperatures, saturation magnetizations obtained from magnetic measurements were found to be compatible with the structural changes caused by reduction temperature.