磁性羧甲基化壳聚糖纳米粒子的制备与表征

以化学共沉淀法制备了Fe3O4纳米粒子,壳聚糖经羧甲基化改性后接枝在Fe3O4颗粒表面,得到了磁性羧甲基化壳聚糖(Fe3O4/CMC)纳米粒子.利用透射电镜(TEM)、X射线衍射(XRD)、傅立叶红外光谱(FT-IR)及磁性测试对产物进行了表征.TEM表明Fe3O4纳米粒子被CMC包覆,粒径约10 nm;XRD分析表明复合纳米粒子中磁性物质为Fe3O4;FT-IR表明壳聚糖发生羧甲基反应以及在Fe3O4表面的接枝反应.Fe3O4/CMC纳米粒子具有超顺磁性,比饱和磁化强度25.73 emu/g,有良好的磁稳定性.     

Preparation and characterization of thermosensitive PNIPAA-coated iron oxide nanoparticles

A new and facile approach was established to fabricate thermoresponsive poly(N-isopropylacrylamide) (PNIPAA) coated iron oxide nanoparticles in a non-aqueous medium. The morphology and structure of the nanoparticle-doped composite were analyzed by?means of transmission electron microscopy (TEM), x-ray powder diffraction (XRD), and Fourier transformation infrared spectrometry (FTIR). The thermosensitivity of the composite was also investigated. Results indicated that the oil-soluble iron oxide nanoparticles encapsulated with PNIPAA, composed of an inorganic iron oxide core and biocompatible PNIPAA shell, were dispersed well in water and had a sphere-like shape. The PNIPAA-coated iron oxide nanoparticles with such a kind of core-shell structure showed excellent thermosensitivity. Namely, the aqueous suspension of PNIPAA-coated iron oxide nanoparticles dramatically changed from transparent to opaque as the temperature increased from room temperature to 38?°C, showing potential as optical transmittance switch materials and their significance in the fields of protein adsorption and purification controlled release, and drug?delivery.     

Magnetically responsive,sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment

This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy‐dispersive X‐ray spectroscopy, and scanning electron microscopy. Then, alginate‐SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4°C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate‐SPION‐sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.Inspec keywords: drug delivery systems, drugs, nanofabrication, magnetic particles, iron compounds, scanning electron microscopy, hyperthermia, biomedical materials, encapsulation, nanoparticles, light scattering, nanomagnetics, cellular biophysics, toxicology, cancer, nanomedicine, superparamagnetism, nanocomposites, magnetometry, paramagnetic resonance, X‐ray chemical analysisOther keywords: sorafenib loaded alginate microspheres, hepatocellular carcinoma treatment, sorafenib loaded magnetic microspheres, superparamagnetic iron oxide nanoparticles, dynamic light scattering, energy‐dispersive X‐ray spectroscopy, scanning electron microscopy, electron spin resonance spectrometer, vibrating sample magnetometer, hyperthermia treatment, drug release, alginate‐SPION‐sorafenib microspheres, antineoplastic agent, cytotoxicity tests, cancerous cells, time 8.0 hour, Fe₃ O₄      

Magnetite-loaded carrier erythrocytes as contrast agents for magnetic resonance imaging

Superparamagnetic iron oxide nanoparticles (SPIONs) are commonly used in magnetic resonance imaging (MRI), but their fast phagocytosis makes them less than ideal for this application. To circumvent the lymphocyte-macrophage system, we encapsulated SPIONs into red blood cells (RBCs). For loading, the RBC's membrane was opened by swelling under hypoosmotic conditions and subsequently resealed. In this work, we demonstrate that SPIONs can be loaded into RBCs in a concentration sufficient to obtain strong contrast enhancement in MRI.     

Synthesis of ordered iron oxide nanoparticle arrays in planar DNA complexes

The formation of iron oxide nanoparticles in planar DNA complexes immobilized on substrates has been studied in reactions involving only biogenic reagents (ferritin and ascorbic acid) in aqueous solutions under normal conditions. Using transmission electron microscopy, we revealed ordered quasi-linear arrays of iron oxide nanoparticles 2–4 nm in diameter, which probably resulted from nanoparticle binding to linear DNA molecules. The electron diffraction patterns of the synthesized nanoparticles are characteristic of polycrystalline magnetic iron oxide (magnetite of maghemite) nanoparticles and point to good crystallinity of the nanoparticles. Our results demonstrate the feasibility of the synthesis of ordered arrays of iron oxide nanoparticles using DNA complexes and may have direct implications for the understanding of biomineralization processes and iron metabolism in living systems.     

Ultrasonic-assisted synthesis and magnetic studies of iron oxide/MCM-41 nanocomposite

Iron oxide nanoparticles were stabilized within the pores of mesoporous silica MCM-41 amino-functionalized by a sonochemical method. Formation of iron oxide nanoparticles inside the mesoporous channels of amino-functionalized MCM-41 was realized by wet impregnation using iron nitrate, followed by calcinations at 550 °C in air. The effect of functionalization level on structural and magnetic properties of obtained nanocomposites was studied. The resulting materials were characterized by powder X-ray diffraction (XRD), high-resolution transmission electron microscopy and selected area electron diffraction (HRTEM and SAED), vibrating sample and superconducting quantum interface magnetometers (VSM and SQUID) and nitrogen adsorption–desorption isotherms measurements. The HRTEM images reveal that the most of the iron oxide nanoparticles were dispersed inside the mesopores of silica matrix and the pore diameter of the amino-functionalized MCM-41 matrix dictates the particle size of iron oxide nanoparticles. The obtained material possesses mesoporous structure and interesting magnetic properties. Saturation magnetization value of magnetic iron oxide nanopatricles stabilized in MCM-41 amino-functionalized by in situ sonochemical synthesis was 1.84 emu g⁻¹. An important finding is that obtained magnetic nanocomposite materials exhibit enhanced magnetic properties than those of iron oxide/MCM-41 nanocomposite obtained by conventional method. The described method is providing a rather short preparation time and a narrow size distribution of iron oxide nanoparticles.     

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.     

In situ synthesis and magnetic studies of iron oxide nanoparticles in calcium-alginate matrix for biomedical applications

In this work we applied a new route to synthesize magnetic iron oxide nanoparticles into alginate polymer for future application as drug delivery system activated by magnetic external stimuli. Calcium-alginate was used to encapsulate iron oxide nanoparticles, and as scaffold for particle nucleation and its influence on particles size and magnetic properties were studied. The iron oxide mean sizes were between 4.3 and 9.5 nm. Iron is dispersed throughout the polymer matrix mainly as iron oxide particles, and a small fraction as iron (III) occupying calcium sites in the polymer network. The temperature dependence of the Mössbauer spectra is typical of superparamagnetic particles in agreement with the magnetic susceptibility data.     

Annealing effects on 5 nm iron oxide nanoparticles

Morphological, structural and magnetic properties of 4.8 nm iron oxide nanoparticles have been investigated after annealing under inert atmosphere at different temperatures. The as-prepared iron oxide nanoparticles have been synthesized by chemical route from high temperature reaction of Fe(acac)3 solution in presence of oleic acid and oleylamine surfactant. Annealing the particles at low temperatures (Tann = 573 K) produces an increment of the mean size from 4.8 nm to 6.0 nm, preserving the same morphology. The coercive field of the annealed sample has a small increasing with respect to the as-prepared sample in agreement with the mean particle volume change. Annealing at higher temperature (Tann = 823 K) leads to a bimodal size distribution of the iron oxide nanoparticles with 6.0 nm and 17 nm mean sizes respectively, where the bigger particles dominate the observed magnetic properties.     

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.     

Surface Engineering of Core/Shell Iron/Iron Oxide Nanoparticles from Microemulsions for Hyperthermia

This paper describes the synthesis and surface engineering of core/shell-type iron/iron oxide nanoparticles for magnetic hyperthermia cancer therapy. Iron/iron oxide nanoparticles were synthesized from microemulsions of NaBH(4) and FeCl(3), followed by surface modification in which a thin hydrophobic hexamethyldisilazane layer - used to protect the iron core - replaced the CTAB coating on the particles. Phosphatidylcholine was then assembled on the nanoparticle surface. The resulting nanocomposite particles have a biocompatible surface and show good stability in both air and aqueous solution. Compared to iron oxide nanoparticles, the nanocomposites show much better heating in an alternating magnetic field. They are good candidates for both hyperthermia and magnetic resonance imaging applications.     

Encapsulation of superparamagnetic iron oxide nanoparticles in poly-(lactide-co-glycolic acid) microspheres for biomedical applications

Magnetic microspheres were prepared using a single step coaxial electrohydrodynamic atomization technique at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the coating and iron oxide (Fe₃O₄) nanoparticles dispersed in polyethylene glycol as the encapsulated material. The morphology and particle size distributions of the prepared magnetic microspheres were investigated by scanning electron microscopy. The particles were spherical with mean diameters ranging from ~ 2 μm to 18 μm, depending on the combination of processing parameters (flow rate and applied voltage). Analysis by infrared spectroscopy and focused ion-beam sectioning confirmed incorporation of iron oxide nanoparticles into the microspheres and the prepared samples were shown to be responsive to an applied magnetic field. This study demonstrates a convenient method for the preparation of nanoparticle loaded microspheres, which could be used potentially as transverse relaxation contrast agents in magnetic resonance imaging, as well as for magnetically guided drug delivery.     

可注射磁性液固相变材料用于骨肉瘤的磁共振成像与低温磁热治疗研究

过高温可诱发肿瘤周围正常组织产生炎症以及热辐射损伤。因此研发一种能在相对较低温度下(例如43 ℃)即可实现肿瘤细胞高致死率的磁性材料对于磁热治疗的临床应用至关重要。本研究聚焦低温、安全、高效磁热疗, 选取FDA批准的液固相变材料聚乳酸-羟基乙酸(PLGA)为原料, 装载一步温和还原法制备得到的超顺磁性氧化铁纳米颗粒, 用于磁共振成像和磁热升温; 进一步在PLGA中装载热休克蛋白HSP90的小分子抑制剂-表没食子儿茶素没食子酸酯(EGCG), 抑制机体受热保护功能, 实现较低温度下杀死肿瘤细胞。体外实验结果表明, 制备得到的超顺磁性氧化铁纳米颗粒不仅拥有良好的T₂加权成像性能, 还具有优良的磁热升温性能。所制备的PLGA/Fe₃O₄/EGCG复合材料在交变磁场下控制升温至43 ℃并保温40 min后发现肿瘤细胞死亡率达70%, 显示出针对骨肉瘤低温磁热治疗的良好潜力。这种可注射磁热相变材料将为骨肉瘤的治疗提供新的思路和材料支撑。     

Inorganic Nanoparticles for MRI Contrast Agents

Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site‐specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle‐based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle‐based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle‐based MRI contrast agents.     

Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging contrast agents or in drug delivery applications. Tissue and cell-specific drug targeting by these nanoparticles can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. In this study, superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared and coupled to insulin for their targeting to cell expressed surface receptors and thereby preventing the endocytosis. The influence of these nanoparticles on human fibroblasts is studied using various techniques to observe cell-nanoparticle interaction that includes light, scanning, and transmission electron microscopy studies. The derivatization of the nanoparticle surface with insulin-induced alterations in cell behavior that were distinct from the underivatized nanoparticles suggests that cell response can be directed via specifically engineered particle surfaces. The results from cell culture studies showed that the uncoated particles were internalized by the fibroblasts due to endocytosis, which resulted in disruption of the cell membrane. In contradiction, insulin-coated nanoparticles attached to the cell membrane, most likely to the cell-expressed surface receptors, and were not endocytosed. The presence of insulin on the surface of the nanoparticles caused an apparent increase in cell proliferation and viability. One major problem with uncoated nanoparticles has been the endocytosis of particles leading to irreversible entry. These results provide a route to prevent this problem. The derivatized nanoparticles show high affinity for cell membrane and opens up new opportunities for magnetic cell separation and recovery that may be of crucial interest for the development of cellular therapies.     

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.     

One-pot size and shape controlled synthesis of DMSO capped iron oxide nanoparticles

We report here the capping of iron oxide nanoparticles with dimethyl sulfoxide (DMSO) to make chloroform soluble iron oxide nanoparticles. Size and shape of the capped iron oxide nanoparticles are well controlled by simply varying the reaction parameters. The synthesized nanocrystallites were characterized by thermal analysis (TG-DTA), powder X-ray diffraction (XRD), transmission electron microscopy (TEM) for evaluating phase, structure and morphology. ¹H NMR spectra of the synthesized samples confirm DMSO, and the capping of DMSO on the ferrite samples. Shift of the S=O stretching frequency in Fourier transformed infra-red (FTIR) spectra indicates that the bonding between DMSO and ferrite is through an oxygen moiety. The magnetic measurements of all the synthesized samples were investigated with a SQUID magnetometer which shows that the magnetic properties are strongly dependent on the size as well as shape of the iron oxide.     

Direct visualization and identification of biofunctionalized nanoparticles using a magnetic atomic force microscope

Because of its outstanding ability to image and manipulate single molecules, atomic force microscopy (AFM) established itself as a fundamental technique in nanobiotechnology. (1) We present a new modality that distinguishes single nanoparticles by the surrounding magnetic field gradient. Diamagnetic gold and superparamagnetic iron oxide nanoparticles become discernible under ambient conditions. Images of proteins, magnetolabeled with nanoparticles, demonstrate the first steps toward a magnetic analogue to fluorescence microscopy, which combines nanoscale lateral resolution of AFM with unambiguous detection of magnetic markers.     

Iron oxide shell as the oxidation-resistant layer in SmCo5 @ Fe2O3 core-shell magnetic nanoparticles

This paper presents a synthesis of magnetic nanoparticles of samarium cobalt alloys and the use of iron oxide as a coating layer to prevent the rapid oxidation of as-made Sm-Co nanoparticles. The colloidal nanoparticles of Sm-Co alloys were made in octyl ether using samarium acetylacetonate and dicobalt octacarbonyl as precursors in a mixture of 1,2-hexadecanediol, oleic acid, and trioctylphosphine oxide (TOPO). Such Sm-Co nanoparticle could be readily oxidized by air and formed a CoO antiferromagnetic layer. Exchange biasing was observed for the surface oxidized nanoparticles. In situ thermal decomposition of iron pentacarbonyl was used to create iron oxide shells on the Sm-Co nanoparticles. The iron oxide shell could prevent Sm-Co nanoparticles from rapid oxidation upon the exposure to air at ambient conditions.     

Synthesis of silica-coated aqueous ferrofluids through ligand exchange with a new organosilica precursor

A new method for the production of aqueous dispersions of superparamagnetic iron oxide nanoparticles with applications in biomedicine is reported. The method is based on the use of a triethoxisilyl dodecanoic acid ligand that has been specially synthesized for this purpose. The nanoparticles were grown in organic medium using oleic acid as surfactant. Subsequently, oleic acid was exchanged for the alkoxysilane ligand, then hydrolysis was performed in a hydrocarbon solvent, and the nanoparticles were transferred into water. The organic and aqueous ferrofluids have been characterized and their magnetic properties have been determined. The resulting maghemite/silica nanoparticles were single core, and stable in aqueous suspension.