Recent Progress in Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size.This review introduces the methods for SPIONs synthesis,including co-precipitation,thermal decomposition,microemulsion and hydrothermal reaction,and surface modification of SPIONs with organometallic and inorganic metals,surface modification for targeted drug delivery,and the use of SPIONs as a contrast agent.In addition,this article also provides an overview of recent progress in SPIONs for the treatment of glioma,lung cancer and breast cancer.

Preparation of Superparamagnetic Dextran-coated Iron Oxide Nanoparticles used as a Novel Gene Carrier into Human Bladder Cancer Cells'

Objective: Application of magnetic nanoparticles as gene carrier in gene therapy has developed quickly. This study was designed to investigate the preparation of superparamagnetic dextran-coated iron oxide nanoparticles (SDION) and the feasibility of SDION used as a novel gene carrier for plasmid DNA in vitro. Methods: SDION were prepared by chemical coprecipitation and separated by gel filtration on Sephacryl S-300HR, characterized by TEM, laser scattering system and Vibrating Sample Magnetometer Signal Processor. The green fluorescent protein (pGFP-C2) plasmid DNA was used as target gene. SDION-pGFP-C2 conjugate compounds were produced by means of oxidoreduction reaction. The connection ratio of SDION and pGFP-C2 DNA was analyzed and evaluated by agarose electrophoresis and the concentration of pGFP-C2 in supernatant was measured. Using liposome as control, the transfection efficiency of SDION and liposome was respectively evaluated under fluorescence microscope in vitro. Results: The diameter of SDION ranges from 3 nm to 8 nm, the effective diameter was 59.2 nm and the saturation magnetization was 0.23 emu/g. After SDION were reasonably oxidized, SDION could connect with pGFP-C2 to a high degree. The transfection efficiency of SDION as gene carrier was higher than that of liposome. Conclusion: The successes in connecting SDION with pGFP-C2 plasmid by means of oxidoreduction reaction and in transferring pGFP-C2 gene into human bladder cancer BIU-87 cells in vitro provided the experimental evidence for the feasibility of SDION used as a novel gene carrier.

Preparation and properties of a nano TiO_2/Fe_3O_4 composite superparamagnetic photocatalyst

Nano TiO2/Fe3O4 composite particles with different molar ratios of TiO2 to Fe3O4 were prepared via sol-gel method. X-ray diffraction, transmission electron microscopy, and vibration sample magnetometry were used to characterize the TiO2/Fe3O4 particles. The photocatalytic activity of the particles was tested by degrading methyl blue solution under UV illumination （254 nm）. The results indicate that with the content of TiO2 increasing, the photocatalytic activity of the composite particles enhances, while the magnetism of the particles decreases. When the molar ratio of TiO2 to Fe3O4 is about 8, both the photocatalytic activity and magnetism of the TiO2/Fe3O4 particles are relatively high, and their photocatalytic activity remains well after repeated use.

Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging

Five types of superparamagnetic iron oxide （SPIO）,i.e. Ferumoxides （Feridex？ Ⅳ, Berlex Laboratories）,Fe r u c a r b o t ra n （ Re s ov i s t？, B aye r H e a l t h c a re ） ,Ferumoxtran-10 （AMI-227 or Code-7227, Combidex？, AMAG Pharma; Sinerem？, Guerbet）, NC100150（Clariscan？, Nycomed,） and （VSOP C184, Ferropharm）have been designed and clinically tested as magneticresonance contrast agents. However, until nowResovist？ is current available in only a few countries.The other four agents have been stopped for furtherdevelopment or withdrawn from the market. AnotherSPIO agent Ferumoxytol （Feraheme） is approved forthe treatment of iron deficiency in adult chronic kidneydisease patients. Ferumoxytol is comprised of ironoxide particles surrounded by a carbohydrate coat, andit is being explored as a potential imaging approach forevaluating lymph nodes and certain liver tumors.

Self-assembled superparamagnetic nanoparticles as MRI contrast agents — A review

Recent progress of the preparation and applications of superparamagnetic iron oxide（SPIO） clusters as magnetic resonance imaging（MRI） probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles（NPs）, especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs＇ size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer（Lb L） capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin（T2） relaxivity and convenience for further functionalization.

In Vitro Targeted Magnetic Delivery and Tracking of Superparamagnetic Iron Oxide Particles Labeled Stem Cells for Articular Cartilage Defect Repair

To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles （SPIO） labeled mesenchymal stem cells （MSCs） density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging （MRI）. Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline （PBS） to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla （T） magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo （SET2WI） sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity （P0.01）. HE staining exibited that a great number of MSCs formed a three-dimensional （3D） cell ＂sheet＂ structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.

Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.

Toxicity of superparamagnetic iron oxide nanoparticles: Research strategies and implications for nanomedicine

Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.

Comparative Study of Images with Pathology:Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Image(MRI)of Splenic VX2 Tumor in Rats

Objective： To establish a rodent model of VX2 tumor of the spleen, to analyze relationship between the change of the signal intensity on superparamagnetic iron oxide enhanced magnetic resonance image （MRI） and pathologic change to evaluate the ability of superparamagnetic iron oxide enhanced MRI for detection of splenic metastases. Methods： 8 rodent models of VX2 tumor of spleen were established successfully. The images were obtained before and after administration of superparamagnetic iron oxide. T1-weighted spin-echo （SE） pulse sequence with a repetition time （TR） of 450 msec, and echo time （TE） of 12 msec （TR/TE=450/12） was used. The imaging parameters of T2-weighted SE pulse sequence were as follows： TR/TE=4000/128. Results： On plain MR scanning T1-weighted splenic VX2 tumor showed hypointensity or isointensity which approximated to the SI of splenic parenchyma. Therefore all lesions were not displayed clearly. On superparamagnetic iron oxide enhancement T2WI sequence the SI of splenic parenchyma decreased obviously with percentage of signal intensity loss （PSIL） of 55.04%, But the SI of tumor was not evidently changed with PSIL of 0.87%. Nevertheless the SNR of normal splenic parenchyma around the lesions had obvious difference （P〈0.001） comparatively. Therefore the contrast between tumor and spleen increased, and tumor displayed more clearly. Moreover the contrast-to-noise （CNR） between VX2 tumor and splenic parenchyma had an evident difference before and after admininstration of superparamagnetic iron oxide （P〈0.001）. Conclusion： On superparamagnetic iron oxide enhancement T1WI sequence the contrast of tumor-to-spleen is poor. Therefore it is not sensitive to characterize the lesions in spleen. On superparamagnetic iron oxide enhanced T2WI the contrast degree of lesions increases obviously. Consequently, superparamagnetic iron oxide -enhanced T2WI MRI scanning can improve the rate of detection and characterization for lesions of spleen.

Superparamagnetic Iron Oxide Labeling of Spinal Cord Neural Stem Cells Genetically Modified by Nerve Growth Factor-β

This study established superparamagnetic iron oxide （SPIO）-labeled nerve growth fac-tor-β （NGF-β） gene-modified spinal cord-derived neural stem cells （NSCs）. The El4 rat embryonic spinal cord-derived NSCs were isolated and cultured. The cells of the third passage were transfected with plasmid pcDNA3-hNGFβ by using FuGENE HD transfection reagent. The expression of NGFβ was measured by immunocytochemistry and Western blotting. The positive clones were selected, allowed to proliferate and then labeled with SPIO, which was mediated by FuGENE HD transfection reagent. Prussian blue staining and transmission electron microscopy （TEM） were used to identify the SPIO particles in the cells. The distinctive markers for stem cells （nestin）, neuron （β-Ⅲ-tubulin）, oligodendrocyte （CNPase） and astrocyte （GFAP） were employed to evaluate the differentiation ability of the labeled cells. The immunocytochemistry and western blotting showed that NGF-β was expressed in spinal cord-derived NSCs. Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells. TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma. The immunocytochemistry demonstrated that the labeled cells were nestin-positive. After differentiation, the cells expressed β-Ⅲ-tubulin, CNPase and GFAP. It was concluded that the SPIO-labeled NGF-β gene-modified spinal cord-derived NSC were successfully established, which are multipotent and capable of self-renewal.

Distribution of c-erbB2 Antisense Probe Labeled with Superparamagnetic Iron Oxide Nanoparticles in the Major Organs of Mice on MR Imaging

Background: The aim of this study was to investigate the distribution of the c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice by MR imaging. Methods: Sixty BALB/c mice were randomly divided into experimental and control groups. MR scans were performed in each mouse of the experimental group at five different time points (10, 30, 60, 180 and 360 min) after injection of the antisense probe. The signal from each major organ (liver, spleen, heart, kidney and muscle tissue) in comparison with the background signal (signal to noise ratio) was determined at each time point as a measure of the distribution of the antisense probe. Six control mice were killed at each of the same time points and the organs immediately removed for determination of their iron content. Results: After injection of the antisense probe, the highest enrichment of the probe was seen in the spleen, reaching a peak at 180 min, followed by the liver, muscle, heart and kidney. Conclusions: MR imaging can visualize the distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice, and this may provide the basis for further in vivo studies of MR imaging time and dose selection.

Magnetic labeling of primary murine monocytes using very small superparamagnetic iron oxide nanoparticles

Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.

Superparamagnetic iron oxide nanoparticles: promote neuronal regenerative capacity?

Currently,we know that neuronal outgrowth during development and regeneration requires a complex interaction of intra-and extracellular molecules such as growth factors,neurotransmitters and extracellular matrix proteins（O’Donnell et al.,2009）.Furthermore,the discovery of a broad spectrum of growth-promoting cues has led to novel concepts for thera-peutic strategies.

Hypoxia Enhances the Therapeutic Potential of Superparamagnetic Iron Oxide-labeled Adipose-derived Stem Cells for Myocardial Infarction

Adipose-derived stem cells（ASCs） induce therapeutic angiogenesis due to pro-angiogenic cytokines secretion. Superparamagnetic iron oxide（SPIO） nanoparticles are critical for magnetic resonance（MR） tracking of implanted cells. Hypoxia is a powerful stimulus for angiogenic activity of ASCs. In this study, we investigated whether therapeutic potency could be enhanced by implantation of hypoxia-preconditioned SPIO-labeled ASCs（SPIOASCs） into the infarcted myocardium. ASCs and SPIOASCs were cultured under 2% O_2（hypoxia） or 95% air（normoxia）. Cells were intramyocardially injected into the infarcted myocardium after 48-h culture. We found that hypoxia culture increased the m RNA expression of hypoxia-inducible factor-1 alpha（HIF-1α） and vascular endothelial growth factor（VEGF） in ASCs and SPIOASCs. The VEGF protein in the conditioned medium was significantly higher in hypoxic ASCs and SPIOASCs than in normoxic ASCs and SPIOASCs. The capillary density and left ventricular contractile function in the infarcted myocardium were significantly higher 4 weeks after implantation with hypoxic ASCs and SPIOASCs than with normoxic ASCs and SPIOASCs. Improvement in the capillary density and left ventricle function didn＇t differ between hypoxic ASCs-transplanted rats and hypoxic SPIOASCs-transplanted rats. Hypoxic culture enhanced the angiogenic efficiency of ASCs. It was concluded that implantation of hypoxic ASCs or SPIOASCs promotes therapeutic angiogenesis and cardiac function recovery in the infarcted myocardium. SPIO labeling does not impact the beneficial effect of hypoxic ASCs.

Growth and differentiation of neural stem cells with superparamagnetic iron oxides labeling in vitro

Objective： To study the growth and differentiation of superparamagnetie iron oxides（SPIOs） labeled neural stem cells （NSCs）. Methods： After NSCs were cultured and subcuhured from newborn rat brain, they were magnetically labeled with ferumoxides （a kind of SPIOs ）. Growth, differentiation and other biology properties of the cells were investigated with immunocytochemistry, transmission electron microscopy （TEM） and Prussian blue staining. Results： Nestin positive cells were found in the culture and offspring clones. NSCs could be differentiated into positive GFAP and NF200 cells in serum culture. When NSCs incubated with ferumoxides, the iron particles were seen in intracellular as well as in offspring clones. With the increase in concentration of ferumoxides （5.6-11.2/μg/ml）, ferumoxides showed no significant difference effects on the growth and differentiation of NSCs. When the concentration of ferumoxides exceeded 22.4μg/ml ,there was significant difference（P〈0.05）. Conclusion： We successfully label NSCs with ferumoxides,it is useful for tracking of magnetic labeled NSCs in vivo with MRI.

Fluorescence detection of Europiumdoped very small superparamagnetic iron oxide nanoparticles in murine hippocampal slice cultures

In the late 1980s,superparamagnetic iron oxide nanoparticles（SPIO）moved into focus as contrast agents in magnetic resonance imaging（MRI）,due to their strong relaxivity and resulting higher resolution of images.At the time,no one anticipated their high potential in basic research or for medical diagnostic andtreatment. Since then, SPIO have been evaluated notonly as spe- cific markers for MRI, but also for cell labeling and tracking （Li et al., 2013）.

高密度磁盘性能优化技术研究综述

在当今数字化时代,海量数据的生成和积累呈现出爆炸式增长的趋势,因此对存储容量的需求急速上升.传统磁记录磁盘CMR因其高容量和低成本而被视为解决海量数据存储的首选.然而,由于超顺磁效应的制约,CMR(Conventional Magnetic Recording)磁盘面密度的提升已触及极限.为了突破这一限制,叠瓦式磁记录技术SMR(Shingled Magnetic Recording)应运而生.基于传统硬盘架构,该技术以重叠磁道的方式,显著提升了磁盘面密度.但SMR磁盘在处理随机写时,会产生不可预测的写放大效应,从而严重影响I/O性能.为解决这一问题,业界随即提出了交错式磁记录技术IMR(Interlaced Magnetic Recording),利用优化的磁道布局和热辅助磁记录技术,有效实现了存储容量与性能的平衡.本文首先详细介绍了SMR和IMR的技术原理和磁盘类型,并量化分析了影响设备I/O性能的关键问题.然后,重点介绍了设备级优化方案,分析并总结了不同策略的优缺点与优化目标.接着,概述了面向设备的系统级和应用级设计方案,如文件系统、独立磁盘阵列技术和数据库等.最后讨论了在未来优化SMR磁盘和IMR磁盘性能可能的研究方向.

基于改进粒子群优化的超顺磁效应多参数提取

时域电磁法中的超顺磁效应一般由磁异常体或磁化层引起,并在响应中后期出现呈近似-1次幂律衰减的慢扩散现象,同时也是地下磁性介质信息的重要表征。传统参数提取方法在对磁性环境的实测数据进行处理时,会由于忽略这种效应导致数据的错误解释。为了实现对含有超顺磁效应数据的准确解释,本文基于改进粒子群优化算法进行了超顺磁效应的多参数提取研究,通过引入Cole-Cole磁化率模型实现了层状超顺磁效应的数值模拟,证明了磁化率、电导率可以影响超顺磁响应的幅值与衰减斜率,并结合改进粒子速度和位置更新策略的粒子群优化算法实现了对磁化率、电导率等参数的提取。结果表明,本文的方法在对超顺磁效应多参数进行提取时最大相对误差不超过2%,验证了方法的有效性。

A nonradiographic strategy to real-time monitor the position of three-dimensional-printed medical orthopedic implants by embedding superparamagnetic Fe_(3)O_(4) particles

Monitoring the position of orthopedic implants in vivo is paramount for enhancing postoperative rehabilitation.Traditional radiographic methods,although effective,pose inconveniences to patients in terms of specialized equipment requirements and delays in rehabilitation adjustment.Here,a nonradiographic design concept for real-time and precisely monitoring the position of in vivo orthopedic implants is presented.The monitoring system encompasses an external magnetic field,a three-dimensional(3D)-printed superparamagnetic intervertebral body fusion cage(SIBFC),and a magnetometer.The SIBFC with a polyetheretherketone framework and a superparamagnetic Fe_(3)O_(4) component was integrally fabricated by the high-temperature selective laser sintering technology.Owing to the superparamagnetic component,the minor migration of SIBFC within the spine would cause the distribution change of the magnetic induction intensities,which can be monitored in real-time by the magnetometer no matter in the static states or dynamic bending motions.Besides horizontal migration,occurrences of intervertebral subsidence in the vertical plane of the vertebrae can also be effectively distinguished based on the obtained characteristic variations of magnetic induction intensities.This strategy exemplifies the potential of superparamagnetic Fe_(3)O_(4) particles in equipping 3D-printed orthopedic implants with wireless monitoring capabilities,holding promise for aiding patients'rehabilitation.

磁响应水凝胶在骨组织工程中的作用与优势

背景:磁响应水凝胶在骨组织工程中具有极大的优势,有利于微创、高效地促进成骨。目的:阐述磁响应水凝胶在骨组织工程领域的应用进展。方法:检索PubMed、Web of Science、万方和中国知网数据库检索相关文献,英文检索词为“Magnetic Hydrogels,Magnetic Nanoparticles,Superparamagnetic Nanoparticles,Fe3O4,SPIONs,Magnetic Fields,Bone Regeneration,Bone Repair,Bone Tissue Engineering”;中文检索词为“磁性水凝胶、磁性纳米粒子、超顺磁性氧化铁纳米粒、磁场、氧化铁纳米粒、骨再生、骨重建、骨修复、骨组织工程”,根据纳入与排除标准对所有文章进行初筛后,最终纳入60篇文章进行综述。结果与结论:①近年来由于磁性纳米粒子的出现,大量的磁响应支架材料被开发出来,其中,含有氧化铁纳米粒子和超顺磁性氧化铁纳米粒子的磁响应水凝胶力学性能突出、生物相容性良好,能够快速响应外部磁场,为种子细胞提供成骨所需的磁机械信号。②磁响应水凝胶可以作为载体精准调控生长因子的释放时机。③基于磁响应水凝胶的三维微环境培养平台下,磁响应水凝胶与细胞之间的界面磁力能够激活细胞表面敏感受体、增强细胞活性、促进新生骨质与宿主骨的整合。④可注射磁响应水凝胶能够应用于骨肿瘤的磁热疗以及生物成像领域。⑤目前,磁响应水凝胶有望模拟出天然骨组织中观察到的各向异性分层结构,然而关于磁响应水凝胶的研究大多集中于体外研究,与体内的局部微环境作用机制仍然不充分。⑥因此,目前基于磁性纳米粒子已经成功地应用于磁共振成像的示踪,未来有望在磁性纳米粒子的性能上优化,构建具有合适降解性能、机械性能和血管功能化的能够实时监测体内变化的磁响应水凝胶。