超顺磁铁氧化物纳米颗粒作为药物载体的研究进展

超顺磁铁氧化物纳米颗粒(SPIONs)是一类合成的小分子γ-氧化铁或四氧化三铁纳米微粒,核直径10～100 nm。SPIONs作为新型药物载体的原理,是在外部磁场诱导下将其导向靶标。该文从SPIONs作为药物运载工具的物化特性,在药物载体方面的应用,以及相关毒理学等方面进行综述。

超顺磁铁粒子的制备及其粒度计算

运用溅射方法,通过控制溅射时间,氩气压强和Al_2O_3与Fe的比例,制备了粒子直径35A—90A的铁超微粒。并对超微粒的粒度进行了计算和电镜观察。

超顺磁磁铁矿磁接收器磁学模型

生物磁铁矿磁接收器理论模型包括单畴磁铁矿磁接收器模型和超顺磁磁铁矿磁接收器模型.蜜蜂体内存在典型的超顺磁磁铁矿颗粒.本文以蜜蜂为例,从磁学理论角度出发,定性的探讨了超顺磁磁铁矿磁接收器的磁学模型和工作机制.在外磁场作用下,每个超顺磁颗粒会受到力的作用,同时伴随着尺寸沿着一定方向的收缩和扩张.超顺磁颗粒把力以及扩张收缩作用传递给外面的生物膜及生物骨架(埋藏在神经系统中)从而产生相应的神经信号,而多个超顺磁颗粒磁接收系统的存在会放大和加强信号的产生.

静电荷、电磁波对蜜蜂影响和CCD相关性

静电荷、电磁波对蜜蜂行为影响尚未见到深入研究和系统的研究报道,就发表的部分观察和实验结果归纳整理,以探其蜜蜂与电磁波(场)之间的奥秘。科学家研究认为,蜜蜂在生命活动中本身能产生电荷并携带电荷,有助于信息传递和更有效地为植物授粉。蜜蜂对电磁波十分敏感,并作出行为上的反应,有待进一步探研与CCD症状发生的相关性。

Pseudolymphoma of the liver associated with primary biliary cirrhosis:A case report and review of literature

We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis.One of the lesions was found incidentally during a medical examination,presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography(CT)after injection of contrast medium.Retrospectively,the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously.Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7.CT during arterial portography revealed two hypointense nodules.Findings with other imaging modalities such as ultrasonography,magnetic resonance imaging,and hepatic angiography were consistent with hepatocellular carcinoma.A right posterior segmentectomy was performed,and the lesions were microscopically diagnosed as pseudolymphoma.To the best of our knowledge,only 31 other cases of this disease have ever been reported,with a highly asymmetrical male:female ratio of 1:9.7.Although we could find only one case of transformation of hepaticpseudolymphoma into lymphoma in the liver,the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully.

A case of hepatic angiomyolipoma difficult to distinguish from hepatocellular carcinoma

We report a case of hepatic angiomyolipoma with uncommon clinical features. A 56-year-old man presented with a hepatic tumor in the caudate lobe. The tumor was hypoechoic on ultrasonography, showed early-phase hyperattenuation on enhanced computed tomography and did not absorb iron on superparamagnetic iron oxide-enhanced magnetic resonance imaging. Hepatocellular carcinoma was highly suspected, and the patient underwent hepatic resection. Histologically, the tumor was mainly composed of smooth muscle cells and contained small amounts of adipose cells and blood vessels. On immunohistochemical staining, the smooth muscle cells were positive for a melanocytic cell-specific monoclonal antibody. In cases with uncommon features of angiomyolipoma, it is quite difficult to distinguish angiomyolipoma from hepatocellular carcinoma.

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma （HCC） in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase.Contrast-enhanced computed tomography （CT） revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase.Magnetic resonance imaging （MRI） revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hvoerintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC.Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically,the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

Substrate temperature dependence of chemical state and magnetoresistance characteristics of Co–TiO2 nanocomposite films

Co−TiO2 nanocomposite films were prepared via magnetron sputtering at various substrate temperatures.The films comprise Co particles dispersed in an amorphous TiO2 matrix and exhibit coexisting ferromagnetic and superparamagnetic properties.When the substrate temperature increases from room temperature to 400℃,Co particles gradually grow,and the degree of Co oxidation significantly decreases.Consequently,the saturation magnetization increases from 0.13 to 0.43 T at the same Co content by increasing the substrate temperature from room temperature to 400℃.At a high substrate temperature,conductive pathways form among some of the clustered Co particles.Thus,resistivity rapidly declines from 1600 to 76μΩ·m.The magnetoresistive characteristic of Co−TiO2 films is achieved even at resistivity of as low as 76μΩ·m.These results reveal that the obtained nanocomposite films have low Co oxidation,high magnetization and magnetoresistance at room temperature.

SPIO-enhanced magnetic resonance imaging for differentiating metastatic from hyperplastic lymph nodes: A study in rabbits

Objective: To investigate the potential of superparamagnetic iron oxide particles (SPIO) in MR imaging for the differentiation between hyperplastic and metastatic lymph node. Methods: Animal models of malignant lymph node metastasis were established in 6 New-Zealand rabbits by a unilateral intra-muscular injection of VX2 carcinoma cells, and models of hyperplastic lymph nodes were induced in another 6 rabbits by a unilateral intra-muscular injection of egg yolk emulsion. MR images of the lymph nodes were obtained before and 12 h after interstitial injection of SPIO. Image results were analyzed and compared with pathological findings. Results: On unenhanced images, the signal intensity of hyperplastic and metastatic lymph nodes did not differ significantly. After administration of SPIO, the signal intensity of both hyperplastic and metastatic lymph nodes remained unchanged on T1-weighted SE images. On T2-weighted SE images, the signal intensity of hyperplastic lymph nodes decreased heterogeneously, while that of all metastatic ones remained unchanged. On T2-weighted GRE images, the signal intensity of hyperplastic lymph nodes decreased significantly and homogeneously, while that of 4 metastatic ones remained unchanged and that of the rest 2 decreased heterogeneously. Conclusion: SPIO-enhanced MR imaging may enable the differentiation between the hyperplastic and metastatic lymph nodes.

蜜蜂体内的磁接收器

很多生物体内存在纳米磁铁矿颗粒,它们为体内的磁接收器奠定了生物物理基础,而磁接收器可以使这些生物能够利用磁场来辨别方位以及方向.蜜蜂腹部同样存在超顺磁磁铁矿颗粒,这些生物磁铁矿粒子尺寸的变化与铁沉积囊泡膜的相互抗拒作用以及与细胞骨架的相互作用组成一个完整的磁接收器系统,可以感觉磁场的变化并诱发神经信号的传递.

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Recently,transplantation of allogeneic and autologous cells has been used for regenerative medicine.A critical issue is monitoring migration and homing of transplanted cells,as well as engraftment efficiency and functional capability in vivo.Monitoring of superparamagnetic iron oxide(SPIO) particles by magnetic resonance imaging(MRI) has been used in animal models and clinical settings to track labeled cells.A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in vivo.Bone marrow mesenchymal stem cells(MSCs) have been extensively investigated for their various therapeutic properties,and exhibit the potential to differentiate into cells of diverse lineages.In this study,cynomolgus monkey MSCs(cMSCs) were labeled with Molday ION Rhodamine-BTM(MIRB),a new SPIO agent,to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in vivo.The results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality imaging.Our method is helpful for detection of transplanted stem cells in vivo,which is required for understanding mechanisms of cell therapy.

In vivo tracing of superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells transplanted for traumatic brain injury by susceptibility weighted imaging in a rat model

Objective：To label rat bone marrow mesenchymal stem cells （BMSCs） with superparamagnetic iron oxide （SPIO） in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury （TBI） by susceptibility weighted imaging （SWI）sequence.Methods：BMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley （SD） rats weighing 200-250 g were randomly divided into 4 groups： Groups A-D （n=6 for each group）. Moderate TBI models of all the rats were developed in the left hemisphere following Feeney＇s method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day,one week and three weeks after implantation.Results： Numerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope （×200）. Scattered little iron particles were observed in the vesicles by electron microscopy （×5000）. MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images,phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.Conclusion：SWI sequence in vivo can consecutively and noninvasively trace and demonstrate the status and distribution of BMSCs labeled with SPIO in the brain of TBI model rats.

Ultrasensitive iron-based magnetic resonance contrast agent constructed with natural polyphenol tannic acid for tumor theranostics

Because of the toxicity of Gd(Ⅲ)complexes and the poor T1 magnetic resonance imaging(MRI)contrast of superparamagnetic iron oxide,the development of new stable,non-toxic,and efficient contrast agents is desirable.Herein,tannic acid(TA),a large natural polyphenol,and bovine serum albumin(BSA)were used to construct non-toxic Fe(Ⅲ)complexes with increased relaxivity based on a strategy slowing the molecular spin.Compared with the commercial T1 contrast agent Magnevist■,TA-Fe@BSA not only exhibits comparable T1 MRI contrast enhancement under 0.5,1 and 7 T magnetic fields both in vitro and in vivo,but also has better stability and biocompatibility.Moreover,TA-Fe@BSA with near-infrared(NIR)absorption demonstrates efficient tumor ablation via photothermal effects.These results demonstrate their strong potential as an alternative T1 MRI contrast agent and tumor theranostics agent in clinical settings.

Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis

Background and objective： It has been shown that macrophages play an important role in the development of severe acute pancreatitis （SAP）, and eventually lead to multiple organ failure （MOF）. Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide （SPIO）-enhanced magnetic resonance imaging （MRI） for diagnosis. Methods： Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome （P） group, and SAP plus SPIO-clodronatecontaining liposome （T） group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase （SAM）, blood urea nitrogen （BUN）, and serum creatinine （SCr） were measured by an automated enzymatic method. Serum tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin （H＆E） staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining. In addition, the macrophage markers （CD68） of the renal tissue were detected with immunohistochemistry. Results： The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups （P〈0.01）. The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group （P〈0.01） and in the T group （P〈0.01）. The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h （P〈0.01）. Conclusions： Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.

The preparation and characteristics of sterically stabilized liposomes containing paclitaxel and super-paramagnetic iron oxide nanoparticles

Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy. In the present study, we selected paclitaxel （PTX） as a therapeutic agent, super-paramagnetic iron oxide nanoparticles （SPIO） as a diagnostic agent and sterically stabilized liposomes as a carrier to prepare theranostic liposomes. The SPIO were prepared and characterized. Moreover, the sterically stabilized liposomes containing PTX and SPIO （PTX/SPIO-SSL） were prepared. The characteristics of PTX/SPIO-SSL were investigated. The results indicated that prepared SPIO exhibited super-paramagnetic and could be used for MRI. The average particle size of PTX/SPIO-SSL was about 170 rim, with a polydispersity index （PDI） less than 0.3. The zeta potential of PTX/SPIO-SSL was negative. The PTX entrapment efficiency of PTX/SPIO-SSL was more than 98%. The TEM results indicated the spherical structure and dense SPIO content in PTX/SPIO-SSL. The in vitro release of PTX from PTX/SPIO-SSL and PTX-SSL was almost identical at both pH 6.8 and 7.4. In conclusion, the PTX/SPIO-SSL were prepared and characterized in vitro. The anti-tumor and diagnostic activity of PTX/SPIO-SSL should be investigated deeply in future study.

Multifunctional dextran micelles as drug delivery carriers and magnetic resonance imaging probes

Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles （SPIO） was prepared for drug delivery and magnetic resonance imaging （MRI）. Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L^-1. Doxorubicin （DOX） and a cluster of the manganese-doped iron oxide nanoparticles （Mn-SPIO） nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplat- lk）rm for the delivery of anticancer drug DOX with a loading content （DLC） of 16 %. Confocal laser scanning microscopy reveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with flee DOX.HCI. Under a 3.0-T MRI scanner, Mn-SPIO/ DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation （T2） rate is also significantly higher than that of the control cells （33.9 versus 2.3 s^-1）. Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.

The effect of neighbor distance of magnetic nanoparticle clusters on magnetic resonance relaxation properties

Superparamagnetic iron oxide （SPIO） nanoparticle clusters are one unique form which can enhance magnetic relaxivity and improve the magnetic resonance imaging contrast at the same iron concentration, comparing to single SPIO nanoparticles. Controlling of cluster size and other structural parameters have drawn great interests in this field to further improve their magnetic properties. In this study, we investigated how the interparticle distance （also known as neighbor distance） of SP10 nanocrystals within clusters affect their magnetic relaxation behaviors. To adjust the neighbor distance, different amount of cholesterol （CHO） was chosen as model spacers embedded into SPIO nanocluster systems with the help of amphiphilic diblock copolymer poly（ethylene glyco）-polyester. Small- angle X-ray scattering was applied to quantify the neighbor distance of SPIO clusters. The results demonstrated that the averaged SPIO nanocrystal neighbor distance of nan- oclusters increased with higher amount of added CHO. Moreover, these SPIO nanocrystal clusters had the promi- nent magnetic relaxation properties. Simultaneously, con- trolling of SPIO nanocrystal neighbor distance can regulate the saturation magnetization （Ms） and magnetic resonance （MR） T2 relaxation of the aggregation, and ultimately obtain better MR contrast effects with decreased neighbor distance.