Poly(amidoamine)-Grafted Superparamagnetic Iron Oxide Nanoparticles: Synthesis and Characterization

In this study, the surface of amino silane modified magnetite nanoparticles were coated with polyamidoamine dendrimer up to the fifth generation via a modified repetitive Michael addition and amidation processes. Products were characterized with X-ray powder diffractometry (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetry (TG), and vibrating sample magnetometry (VSM) which proved the superparamagnetic properties of all products. The attachment of silane group and PAMAM (poly(amidoamine) dendrimers on the surface of the magnetite nanoparticles were confirmed with both TG and FT-IR. Due to the given saturation magnetization (M _s) of the products, they may be a powerful tool for biomedical applications and catalysis chemistry.     

Preparation and Application of Amino- and Dextran-Modified Superparamagnetic Iron Oxide Nanoparticles

Amino-dextran-functionalized superparamagnetic iron oxide nanoparticles (SPION) were synthesized by two-steps: Dextran-modified SPION was obtained by “one-step” co-precipitation method. Then, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAPS) was added to the resultant dextran-SPION to prepare amino-dextran-functionalized SPION (AEAPS/Dex-SPION). The particles were characterized by vibrating sample magnetometer (VSM), transmission electron micrographs (TEM), atomic force micrographs (AFM), gas chromatography and atomic absorption spectrophotometry. The size of the modified particles varied in a range of 30 to 40 nm and did not change significantly after modification. The binding rate of AEAPS was 91.15%. A monoclonal antibody against S100 (anti-S-100), a gold standard for the diagnosis of melanocytic lesions, was conjugated to the AEAPS/Dex-SPION to prepare immuno-SPION. From the result in melanoma B16 cell, the immuno-SPION was proven to have a bio-targeting activity. Such AEAPS/Dex-SPION might be very useful for bio-magnetically targeted detection in early melanocytic lesions.     

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.     

Surface Functionalization of Single Superparamagnetic Iron Oxide Nanoparticles for Targeted Magnetic Resonance Imaging

Magnetic resonance imaging (MRI), a non‐invasive, non‐radiative technique, is thought to lead to cellular or even molecular resolution if optimized targeted MR contrast agents are introduced. This would allow diagnosing progressive diseases in early stages. Here, it is shown that the high binding affinity of poly(ethylene glycol)‐gallol (PEG‐gallol) allows freeze drying and re‐dispersion of 9 ± 2‐nm iron oxide cores individually stabilized with ≈9‐nm‐thick stealth coatings, yielding particle stability for at least 20 months. Particle size, stability, and magnetic properties of PEGylated particles are compared to Feridex, a commercially available untargeted negative MR contrast agent. Biotin‐PEG(3400)‐gallol/methoxy‐PEG(550)‐gallol stabilized nanoparticles are further functionalized with biotinylated human anti‐VCAM‐1 antibodies using the biotin–neutravidin linkage. Binding kinetics and excellent specificity of these nanoparticles are demonstrated using quartz crystal microbalance with dissipation monitoring (QCM‐D). These MR contrast agents can be functionalized with any biotinylated ligand at controlled ligand surface density, rendering them a versatile research tool.     

Magnetic Targeting of Human Mesenchymal Stem Cells with Internalized Superparamagnetic Iron Oxide Nanoparticles

Cell therapies offer exciting new opportunities for effectively treating many human diseases. However, delivery of therapeutic cells by intravenous injection, while convenient, relies on the relatively inefficient process of homing of cells to sites of injury. To address this limitation, a novel strategy has been developed to load cells with superparamagnetic iron oxide nanoparticles (SPIOs), and to attract them to specific sites within the body by applying an external magnetic field. The feasibility of this approach is demonstrated using human mesenchymal stem cells (hMSCs), which may have a significant potential for regenerative cell therapies due to their ease of isolation from autologous tissues, and their ability to differentiate into various lineages and modulate their paracrine activity in response to the microenvironment. The efficient loading of hMSCs with polyethylene glycol‐coated SPIOs is achieved, and it is found that SPIOs are localized primarily in secondary lysosomes of hMSCs and are not toxic to the cells. Further, the key stem cell characteristics, including the immunophenotype of hMSCs and their ability to differentiate, are not altered by SPIO loading. Through both experimentation and mathematical modeling, it is shown that, under applied magnetic field gradients, SPIO‐containing cells can be localized both in vitro and in vivo. The results suggest that, by loading SPIOs into hMSCs and applying appropriate magnetic field gradients, it is possible to target hMSCs to particular vascular networks.     

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.     

超顺磁单分散性Fe3O4磁纳米粒的制备及性能表征

具有超顺磁单分散性的Fe₃O₄磁纳米粒在生物医学材料领域有着广泛的用途. 本研究在水、乙醇和甲苯混合体系74℃回流的条件下制备了具有超顺磁性的表面含油酸的Fe₃O₄磁纳米粒,研究了制备过程中OH^-浓度的变化对磁纳米粒的表面性能、粒径、分散性及磁性能的影响, 并对其机理进行了初步探讨. 采用XRD、FTIR、DLS、TEM和VSM等手段对制备的磁纳米粒进行表征. 结果表明, 当NaOH/Fe(Ⅱ)摩尔比＜8时, Fe₃O₄磁纳米粒表面含油酸可良好地分散于非极性溶剂中, NaOH的加入对磁纳米粒的粒径和饱和磁化强度等性能无明显影响;而当NaOH/Fe(Ⅱ)摩尔比≥8时, Fe₃O₄磁纳米粒仅能分散于水等极性溶剂中, 饱和磁化强度虽可增至40A·m²/kg, 但为多分散且易团聚.     

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．     

Superparamagnetic Behavior of Zinc-Substituted Nickel Ferrite Nanoparticles and its Effect on Mossbauer and Magnetic Parameters

Zinc-substituted nickel ferrite (Ni _1?x Zn _x Fe ₂ O ₄ with x = 0.0, 0.2, 0.4, 0.6, 0.8, and 1.0) nanoparticles were synthesized by solgel auto-combustion technique at low temperature and characterized by using X-ray diffraction, scanning electron microscopy, pulse field hysteresis loop technique, and Mossbauer spectroscopy. X-ray diffraction studies confirmed the formation of single-phase spinel structure of the prepared ferrite samples with average crystallite size of 30 nm, very close to that of the critical size for nanoparticles exhibiting superparamagnetism. Scanning electron micrographs of the ferrite samples showed uniform spherical morphology of nanograins with homogenous microstructure. Further investigations on magnetic properties by pulse field hysteresis loop technique and Mossbauer spectroscopy indicated the presence of superparamagnetic phases in the ferrite samples attributed to occupation of octahedral [B] sites by zinc ions in these Ni–Zn samples and also to the nanometer sizes of the ferrite particles. Magnetic behavior of the Ni–Zn ferrite system is in agreement, initially, with Neel’s two-sublattice collinear model and then with the Yafet–Kittel model for samples with higher zinc content (x ≥ 0.4). Value of hyperfine splitting is found to decrease with increase in zinc content and is attributed to the reduction in particle size giving rise to superparamagnetism. Other Mossbauer parameters like quadrupole splitting and the isomer shift are within the reported range for those of ferrites with spinel structure.     

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.     

Effect of Carbon Shell on the Structural and Magnetic Properties of Fe3O4 Superparamagnetic Nanoparticles

Carbon-encapsulated iron oxides (Fe₃O₄/C) with a core/shell structure have been successfully synthesized by using a simple two-step hydrothermal method at 180 ^°C. Fe₃O₄ core nanoparticles were prepared by coprecipitation under two conditions. Synthesized nanoparticles were characterized by transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. TEM images and FTIR results prove that carbon coated iron oxide is formed and the estimated size for most of them is below 11 nm, which was consistent with the XRD result. The Williamson–Hall (W–H) method has been used to calculate crystallite sizes and lattice strain based on the peak broadening of the Fe₃O₄ and Fe₃O₄/C nanoparticles. The results of VSM imply that the Fe₃O₄ core and core–shell nanoparticles are superparamagnetic. The saturation magnetization of Fe₃O₄ and Fe₃O₄/C are 49 emu/gr and 40 emu/gr, respectively. The magnetic behaviors reveal that the amorphous carbon shell can decrease the saturation magnetization of Fe₃O₄ nanoparticles due to core–shell interface effects and shielding.     

超顺磁单分散性Fe3O4磁纳米粒的制备及性能表征

具有超顺磁单分散性的Fe₃O₄磁纳米粒在生物医学材料领域有着广泛的用途. 本研究在水、乙醇和甲苯混合体系74℃回流的条件下制备了具有超顺磁性的表面含油酸的Fe₃O₄磁纳米粒,研究了制备过程中OH^-浓度的变化对磁纳米粒的表面性能、粒径、分散性及磁性能的影响, 并对其机理进行了初步探讨. 采用XRD、FTIR、DLS、TEM和VSM等手段对制备的磁纳米粒进行表征. 结果表明, 当NaOH/Fe(Ⅱ)摩尔比＜8时, Fe₃O₄磁纳米粒表面含油酸可良好地分散于非极性溶剂中, NaOH的加入对磁纳米粒的粒径和饱和磁化强度等性能无明显影响;而当NaOH/Fe(Ⅱ)摩尔比≥8时, Fe₃O₄磁纳米粒仅能分散于水等极性溶剂中, 饱和磁化强度虽可增至40A·m²/kg, 但为多分散且易团聚.     

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.