葡聚糖中超顺磁氧化铁复合纳米粒子制备影响因素及表征

利用化学共沉积法在改性葡聚糖体系下制备了以超顺磁性纳米氧化铁为核心，外包葡聚糖的壳核结构复合粒子．对制备过程控制因素进行了详细的研究，实验结果表明：利用改性葡聚糖为表面活性剂，碱源快速滴加，合理的控制反应时间，温度可形成小核的超顺磁性纳米氧化铁-葡聚糖复合纳米粒子．在优化的实验条件下，得到核心的平均粒径5nm，总体的平均粒径为7．8nm，并利用XRD、TEM和GLS等手段对其结构，形态和粒径分布进行了表征．     

非水介质中制备纳米氧化铁

在严格无水的条件下,制备了氧化铁纳米粒子,采用FTIR、XRD、TEM、TG-DTA、Mossbauer谱等方法对所得的纳米粒子进行了表征和分析.实验结果证明:室温晾干后,得到无定形的FeOOH超细粉体;通过控制热处理的温度;可以得到不同晶型的氧化铁纳米粒子.即:在300℃热处理1h,主要得到约30nm的Fe_3-xO₄,450℃处理1h,可得到粒径约为98nnm的α-Fe₂O₃粒子.     

Amino‐polyvinyl Alcohol Coated Superparamagnetic Iron Oxide Nanoparticles are Suitable for Monitoring of Human Mesenchymal Stromal Cells In Vivo

Mesenchymal stromal cells (MSCs) are promising candidates in regenerative cell‐therapies. However, optimizing their number and route of delivery remains a critical issue, which can be addressed by monitoring the MSCs’ bio‐distribution in vivo using super‐paramagnetic iron‐oxide nanoparticles (SPIONs). In this study, amino‐polyvinyl alcohol coated (A‐PVA) SPIONs are introduced for cell‐labeling and visualization by magnetic resonance imaging (MRI) of human MSCs. Size and surface charge of A‐PVA‐SPIONs differ depending on their solvent. Under MSC‐labeling conditions, A‐PVA‐SPIONs have a hydrodynamic diameter of 42 ± 2 nm and a negative Zeta potential of 25 ± 5 mV, which enable efficient internalization by MSCs without the need to use transfection agents. Transmission X‐ray microscopy localizes A‐PVA‐SPIONs in intracellular vesicles and as cytosolic single particles. After identifying non‐interfering cell‐assays and determining the delivered and cellular dose, in addition to the administered dose, A‐PVA‐SPIONs are found to be non‐toxic to MSCs and non‐destructive towards their multi‐lineage differentiation potential. Surprisingly, MSC migration is increased. In MRI, A‐PVA‐SPION‐labeled MSCs are successfully visualized in vitro and in vivo. In conclusion, A‐PVA‐SPIONs have no unfavorable influences on MSCs, although it becomes evident how sensitive their functional behavior is towards SPION‐labeling. And A‐PVA‐SPIONs allow MSC‐monitoring in vivo.     

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。     

Characterizing Physical Properties of Superparamagnetic Nanoparticles in Liquid Phase Using Brownian Relaxation

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used as bioimaging contrast agents, heating sources for tumor therapy, and carriers for controlled drug delivery and release to target organs and tissues. These applications require elaborate tuning of the physical and magnetic properties of the SPIONs. The authors present here a search‐coil‐based method to characterize these properties. The nonlinear magnetic response of SPIONs to alternating current magnetic fields induces harmonic signals that contain information of these nanoparticles. By analyzing the phase lag and harmonic ratios in the SPIONs, the authors can predict the saturation magnetization, the average hydrodynamic size, the dominating relaxation processes of SPIONs, and the distinction between single‐ and multicore particles. The numerical simulations reveal that the harmonic ratios are inversely proportional to saturation magnetizations and core diameters of SPIONs, and that the phase lag is dependent on the hydrodynamic volumes of SPIONs, which corroborate the experimental results. Herein, the authors stress the feasibility of using search coils as a method to characterize physical and magnetic properties of SPIONs, which may be applied as building blocks in nanoparticle characterization devices.     

Anti-Platelet Effect Induced by Iron Oxide Nanoparticles: Correlation with Conformational Change in Fibrinogen

Iron oxide nanoparticles are developed for various biomedical applications, however, there is limited understanding regarding their effects and toxicity on blood components. The particles traveling in circulation inevitably interact with blood cells and plasma proteins and may interfere with hemostasis. Specifically, this study focuses on the influence of superparamagnetic iron oxide nanoparticles (SPIONs) coated with a biocompatible polymer, polyvinyl alcohol (PVA), on platelet function. Here, engineered SPIONs that are functionalized with various PVA coatings to provide these particles with different surface charges and polymer packing are described. These formulations are assessed for any interference with human platelet functions and coagulation, ex vivo. Positively charged SPIONs induce a significant change in platelet GPIIb-IIIa conformation, indicative of platelet activation at the dose of 500 µg mL⁻¹. Remarkably, engineered PVA(polyvinyl alcohol)-SPIONs all display a robust dose-dependent anti-platelet effect on platelet aggregation, regardless of the PVA charge and molecular weight. After assessing hypotheses involving SPION-induced steric hindrance in platelet–platelet bridging, as well as protein corona involvement in the antiplatelet effect, the study concludes that the presence of PVA-SPIONs induces fibrinogen conformational change, which correlates with the observed dose-dependent anti-platelet effect.     

Ferritin Protein Regulates the Degradation of Iron Oxide Nanoparticles

Proteins implicated in iron homeostasis are assumed to be also involved in the cellular processing of iron oxide nanoparticles. In this work, the role of an endogenous iron storage protein—namely the ferritin—is examined in the remediation and biodegradation of magnetic iron oxide nanoparticles. Previous in vivo studies suggest the intracellular transfer of the iron ions released during the degradation of nanoparticles to endogenous protein cages within lysosomal compartments. Here, the capacity of ferritin cages to accommodate and store the degradation products of nanoparticles is investigated in vitro in the physiological acidic environment of the lysosomes. Moreover, it is questioned whether ferritin proteins can play an active role in the degradation of the nanoparticles. The magnetic, colloidal, and structural follow‐up of iron oxide nanoparticles and proteins in lysosome‐like medium confirms the efficient remediation of potentially harmful iron ions generated by nanoparticles within ferritins. The presence of ferritins, however, delays the degradation of particles due to a complex colloidal behavior of the mixture in acidic medium. This study exemplifies the important implications of intracellular proteins in processes of degradation and metabolization of iron oxide nanoparticles.     

Epirubicin‐Loaded Superparamagnetic Iron‐Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron‐oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI–SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI–SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g^?1. They feature specific pH‐sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose‐dependent. In vitro transdermal studies demonstrate that the EPI–SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic‐field‐assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION‐based vector for feasible transdermal therapy of skin cancer.     

MPEG修饰的纳米氧化铁粒子的合成及清洗工艺

以MPEG为溶剂、还原剂及修饰剂,Fe(acac)3为铁源,通过高温热分解法制备了超顺磁性氧化铁纳米粒子(SPIONs).采用饱和食盐水清洗方法对合成的粒子进行收集,经透析除去其表面残留的NaCl.采用XRD,TEM,HRTEM,SQUID,ICP MS,TGA,FT IR,纳米粒度与Zeta电位分析仪对样品进行表征.结果表明:经透析处理后氧化铁的质量分数为NaCl的6.9×104倍,制备的SPIONs具有高的结晶度及单分散性,在300K下,具有超顺磁性,饱和磁化强度为53.7A· m2·kg-1;具有惰性端基的MPEG修饰于SPIONs表面,为其提供了良好的水分散性.采用盐桥法萃取清洗工艺可清除过量的MPEG,有利于SPIONs更好的应用在生物医学领域.     

用原子力显微镜研究葡聚糖包覆纳米氧化铁微粒的形貌特征

采用化学共沉淀法合成了葡聚糖包覆的超顺磁纳米氧化铁微粒,用原子力显微镜对其分布状态、微粒形貌和尺度等进行了表征,并与透射电镜观察结果进行了比较。结果表明：葡聚糖包覆的超顺磁纳米氧化铁微粒大小均匀且有规律的定向分布,无团聚现象;透射电镜显示其核心氧化铁纳米粒子的外形主要为不规则的球形,粒径5～20nm被葡聚糖包覆后的纳米氧化铁微粒呈长方体,尺寸为（200-300）nm×（400-600）nm×（50-70）nm。     

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。     

Photoacoustic‐Guided Surgery with Indocyanine Green‐Coated Superparamagnetic Iron Oxide Nanoparticle Clusters

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real‐time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles—with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20–30% of the total weight (ICG + SPIO). The ICG–SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG–SPIO clusters, animals undergoing PA‐guided surgery demonstrate increased progression‐free survival compared to animals undergoing microscopic surgery.     

Superparamagnetic Iron Oxide Nanoparticles (SPION) for the Treatment of Antibiotic‐Resistant Biofilms

Bacterial infections caused by antibiotic‐resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free‐floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two‐step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today.     

Interactions of Mitoxantrone-Modified Superparamagnetic Iron Oxide Nanoparticles with Biomimetic Membranes and Cells

We report on the formation of conjugates of superparamagnetic iron nanoparticles(NPs)with the chemotherapeutic agent mitroxantrone(MTX).The NPs are synthesized from mixed iron oxides and are ca.15 nm in diameter.Decoration of the NP surface with MTX is accomplished with standard coupling chemistry techniques using sebacic acid as the coupling agent.The resulting NP-MTX conjugate is characterized thermogravimetrically,spectroscopically and electrochemically.The interactions of the NP-MTX conjugate with a model lipid layer formed as a Langmuir-Blodgett(LB)film reveal that the nanoparticle exhibits a significant perturbative effect on the layer,as seen from translational diffusion(FRAP)measurements.Evaluation of the cytotoxicity of the conjugate relative to that of free MTX demonstrates that the NP-MTX conjugate is more toxic than free MTX for both normal and malignant cell lines.These results underscore the importance of targeted delivery in the administration of chemotherapeutic agents.