In vivo biodistribution,antioxidant and hemolysis tendency of superparamagnetic iron oxide nanoparticles – Potential anticancer agents

Ferromagnetic and superparamagnetic oxide nanoparticles are of particular attention because of their possible use in various fields ranging from bio-nanotechnology to spintronics. Detailed magnetic, dielectric and impedance investigations are crucial for the above-mentioned applications. This study deals with the exploration of various iron oxide phases under as-synthesized conditions by sol–gel method. pH of the sols is varied in the range of 1 to 11. X-ray diffraction (XRD) analysis indicate amorphous behavior for nanoparticles synthesized using pH 1 and 3. Nanoparticles synthesized using pH 2 and 4–6 exhibit hematite phase of iron oxide. Whereas structural transition to maghemite phase is observed for pH 7–8. Nanoparticles synthesized using high pH values, i.e. 9–11, exhibit structural transition towards magnetite phase of iron oxide. Hematite nanoparticles exhibit superparamagnetic and ferromagnetic hysteresis curves with saturation magnetization of ～ 24 emu/g and ～ 13–17 emu/g at pH 2 and pH 4–6, respectively. Maghemite nanoparticles exhibit superparamagnetic (pH 7) and ferromagnetic (pH 8) response with saturation magnetization of ～ 69 and ～ 42 emu/g, respectively. Fe₃O₄ nanoparticles exhibit superparamagnetic (pH 9–10) and ferromagnetic (pH 11) behavior with saturation magnetization of ～ 88, 87 and 52 emu/g, respectively. High grain boundary resistance contributed towards high dielectric constant of ～ 99, 109 and 154 (log f = 5.0) at pH 2, 7 and 9. Detailed impedance values indicate dominant role of grain boundaries in the conductivity of iron oxide nanoparticles. Superparamagnetic iron oxide (pH 9) exhibits strong antioxidant activity along with a very weak hemolytic response. The findings of cell lysis reveal that synthesized nanoparticles have a potential to combat dangerous cancer cells. Drug efficacy results show that after 120 min the encapsulation efficacy reaches a peak of ～ 83 % using curcumin, a naturally existing drug. In vivo biodistribution of nanoparticles was studied in Rabbit model. Synthesized nanoparticles are labelled using Technetium-99 m. Whereas, labeling efficacy and stability was examined using =nstant thin layer chromatography (ITLC) process. In vitro and in vivo results suggest potential anti-cancer applications of as-synthesized superparamagnetic nanoparticles.     

Magnetic mesoporous carbon for efficient removal of organic pollutants

Carbon materials such as activated carbons have been used in the field of water and wastewater treatments. However, the lack of mesopore and, particularly, the difficulty in recovering the spent carbon limited their applications. In this work, magnetic mesoporous carbon microspheres were synthesized by impregnating iron oxide precursors in the mesoporous carbon followed by the in situ conversion of the precursors into magnetite nanoparticles. The as-synthesized carbon microspheres with a high surface area of 742?m²/g and large mesopores of ～4.4?nm exhibited an excellent adsorption capacity for aqueous organic pollutants. The superparamagnetic microspheres with a saturation magnetization of 7.15 emu/g can be easily separated from the treated solution by external magnetic field.     

Thermal Plasma Synthesis of Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles were synthesized by injecting ferrocene vapor and oxygen into an argon/helium DC thermal plasma. Size distributions of particles in the reactor exhaust were measured online using an aerosol extraction probe interfaced to a scanning mobility particle sizer, and particles were collected on transmission electron microscopy (TEM) grids and glass fiber filters for off-line characterization. The morphology, chemical and phase composition of the nanoparticles were characterized using TEM and X-ray diffraction, and the magnetic properties of the particles were analyzed with a vibrating sample magnetometer and a magnetic property measurement system. Aerosol at the reactor exhaust consisted of both single nanocrystals and small agglomerates, with a modal mobility diameter of 8?C9?nm. Powder synthesized with optimum oxygen flow rate consisted primarily of magnetite (Fe₃O₄), and had a room-temperature saturation magnetization of 40.15 emu/g, with a coercivity and remanence of 26 Oe and 1.5 emu/g, respectively.     

Synthesis and characterization of poly(divinylbenzene)-coated magnetic iron oxide nanoparticles as precursor for the formation of air-stable carbon-coated iron crystalline nanoparticles

Maghemite (gamma-Fe2O3) nanoparticles of 15 +/- 3 nm diameter were prepared by nucleation of gelatin/iron oxide followed by growth of gamma-Fe2O3 films onto these nuclei. The gamma-Fe2O3 nanoparticles were coated with polydivinylbenzene (PDVB) by emulsion polymerization of divinylbenzene (DVB) in an aqueous continuous phase containing the gamma-Fe2O3 nanoparticles. The PDVB-coated gamma-Fe2O3 nanoparticles, dispersed in water, were separated from homo-PDVB nanoparticles using the high gradient magnetic field (HGMF) technique. The influence of DVB concentration on the amount of PDVB coating, on the size and size distribution of the coated gamma-Fe2O3 nanoparticles and on their magnetic properties, has been investigated. Air-stable carbon-coated iron (alpha-Fe/C) crystalline nanoparticles of 41 +/- 12 nm diameter have been prepared by annealing the PDVB-coated gamma-Fe2O3 nanoparticles at 1050 degrees C in an inert atmosphere. These nanoparticles exhibit high saturation magnetization value (83 emu g(-1)) and excellent resistance to oxidation. Characterization of the PDVB-coated gamma-Fe2O3 and of the alpha-Fe/C nanoparticles has been accomplished by TEM, HRTEM, DLS, FTIR, XRD, thermal analysis, zeta-potential, and magnetic measurements.     

High Coercivity Induced in Nickel Ferrite Nanoparticles by Mechanical Milling

This work reports a study of the structure and magnetic behavior of NiFe₂O₄ ferromagnetic oxide nanoparticles synthesized by the combustion method. The structural and magnetic properties of nanoparticles after mechanical milling are investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy, transmission electron microscope. Their structural properties and magnetic behavior are characterized by a vibrating sample magnetometer (VSM). The non-milled sample presents a coercivity of 89 Oe, a saturation magnetization of 69 emu/g, and a remanence of 13 emu/g. After milling, the sample attains the coercivity, the saturation magnetization, and the remanence of 160.7 Oe, 56 emu/g, and 12.8 emu/g respectively. The porosity estimated from the X-ray density and bulk density is about 35%. The XRD analysis by Stokes–Wilson, Williamson-Hall, and dislocation density equations are used to estimate strain and the dislocation density induced by mechanical milling in the sample.     

Synthesis and characterization of enzyme-magnetic nanoparticle complexes: effect of size on activity and recovery

The influence of particle size on the activity and recycling capabilities of enzyme conjugated magnetic nanoparticles was studied. Co-precipitation and oxidation of Fe(OH)(2) methods were used to fabricate three different sizes of magnetic nanoparticles (5 nm, 26 nm and 51 nm). Glucose oxidase was covalently bound to the magnetic nanoparticles by modifying the surfaces with 3-(aminopropyl)triethoxysilane (APTES) and a common protein crosslinking agent, glutaraldehyde. Analysis by Transmission Electron Microscopy (TEM) showed that the morphology of the magnetic nanoparticles to be spherical and sizes agreed with results of the Brunauer, Emmett, and Teller (BET) method. Magnetic strength of the nanoparticles was analyzed by magnetometry and found to be 49 emu g(-1) (5 nm), 73 emu g(-1) (26 nm), and 85 emu g(-1) (51 nm). X-ray photoelectron spectroscopy (XPS) confirmed each step of the magnetic nanoparticle surface modification and successful glucose oxidase binding. The immobilized enzymes retained 15-23% of the native GOx activity. Recycling stability studies showed approximately 20% of activity loss for the large (51 nm) and medium (26 nm) size glucose oxidase-magnetic nanoparticle (GOx-MNP) bioconjugate and about 96% activity loss for the smallest GOx-MNP bioconjugate (5 nm) after ten cycles. The bioconjugates demonstrated equivalent total product conversions as a single reaction of an equivalent amount of the native enzyme after the 5th cycle for the 26 nm nanoparticles and the 7th cycle for the 51 nm nanoparticles.     

Temperature-responsive magnetite/PEO-PPO-PEO block copolymer nanoparticles for controlled drug targeting delivery

In this study, temperature-responsive magnetite/polymer nanoparticles were developed from iron oxide nanoparticles and poly(ethyleneimine)-modified poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer. The particles were characterized by TEM, XRD, DLS, VSM, FTIR, and TGA. A typical product has an approximately 20 nm magnetite core and an approximately 40 nm hydrodynamic diameter with a narrow size distribution and is superparamagnetic with large saturation magnetization (51.34 emu/g) at room temperature. The most attractive feature of the nanoparticles is their temperature-responsive volume-transition property. DLS results indicated that their average hydrodynamic diameter underwent a sharp decrease from 45 to 25 nm while evaluating the temperature from 20 to 35 degrees C. The temperature-dependent evolution of the C-O stretching band in the FTIR spectra of the aqueous nanoparticles solution revealed that thermo-induced self-assembly of the immobilized block copolymers occurred on the magnetite solid surfaces, which is accompanied by a conformational change from a fully extended state to a highly coiled state of the copolymer. Consequently, the copolymer shell could act as a temperature-controlled "gate" for the transit of guest substance. The uptake and release of both hydrophobic and hydrophilic model drugs were well controlled by switching the transient opening and closing of the polymer shell at different temperatures. A sustained release of about 3 days was achieved in simulated human body conditions. In primary mouse experiments, drug-entrapped magnetic nanoparticles showed good biocompatibility and effective therapy for spinal cord damage. Such intelligent magnetic nanoparticles are attractive candidates for widespread biomedical applications, particularly in controlled drug-targeting delivery.     

Synthesis of monodisperse biotinylated p(NIPAAm)-coated iron oxide magnetic nanoparticles and their bioconjugation to streptavidin

We describe here the synthesis of 10 nm, monodisperse, iron oxide nanoparticles that we have coated with temperature-sensitive, biotinylated p(NIPAAm) (b-PNIPAAm). The PNIPAAm was prepared by the reversible addition fragmentation chain transfer polymerization (RAFT), and one end was biotinylated with a PEO maleimide-activated biotin to form a stable thioether linkage. The original synthesized iron oxide particles were stabilized with oleic acid. They were dispersed in dioxane, and the oleic acid molecules were then reversibly exchanged with a mixture of PNIPAAm and b-PNIPAAm at 60 degrees C. The b-PNIPAAm-coated magnetic nanoparticles were found to have an average diameter of approximately 15 nm by dynamic light scattering and transmission electron microscopy. The ability of the biotin terminal groups on the b-PNIPAAm-coated nanoparticles to interact with streptavidin was confirmed by fluorescence and surface plasmon resonance. It was found that the b-PNIPAAm-coated iron oxide nanoparticles can still bind with high affinity to streptavidin in solution or when the streptavidin is immobilized on a surface. We have also demonstrated that the binding of the biotin ligands on the surface of the temperature-responsive magnetic nanoparticles to streptavidin can be turned on and off as a function of temperature.     

原位沉析法制备磁性氧化铁羟基磷灰石/壳聚糖棒材

首先通过化学沉淀法制备磁性氧化铁羟基磷灰石(Fe3O4/HA),然后以壳聚糖(CS)为基体,利用原位沉析法将Fe3O4/HA与CS复合,制得磁性Fe3O4/HA/CS复合材料.经XRD、粒径分布和PPMS测试,结果表明了Fe3O4/HA复合物的生成.系统研究了磁性Fe3O4/HA/CS棒材力学性能的影响因素,最终确定Fe3O4与HA质量比为3∶17,磁性Fe3O4/HA与CS质量比为9∶91时,棒材的力学性能最优,弯曲强度可达到87.0 MPa,弯曲模量1.57 GPa.     

羟丙基-β-环糊精磁性复合微粒的合成及作为阿霉素载体的体外释药研究

羟丙基-β-环糊精因具有内部疏水和外部亲水锥形圆筒空腔结构和良好的生物相容性在磁性药物载体方面有潜在应用价值。本研究将羟丙基-β-环糊精修饰在超顺磁性纳米四氧化三铁粒子表面制备磁性复合微粒,用红外光谱,透射电镜,振动磁强计,电感耦合等离子发射等方法对该复合微粒进行了表征,并将其用于抗肿瘤药物阿霉素的体外载药与释药实验研究。结果表明该复合微粒的粒径大小在10-20nm,饱和磁化强度59.9 emu/g,铁含量55.4%。对阿霉素的载药量为87.8 μg/mg。体外释药结果显示载药复合粒子在PBS中1天,4天,10天的累积释药量分别为35.5%, 49.3%, 76.5%,表明该载体具有一定的药物缓释功能。由此可知,羟丙基-β-环糊精磁性复合微粒可作为磁性靶向给药系统的有效载体。     

Biocompatible and biodegradable polymer nanofibers displaying superparamagnetic properties.

Superparamagnetic polymer nanofibers intended for drug delivery and therapy are considered here. Magnetite (Fe3O4) nanoparticles in the diameter range of 5-10 nm were synthesized in aqueous solution. Polymer nanofibers containing magnetite nanoparticles were prepared from commercially available poly(hydroxyethyl methacrylate), PHEMA, and poly-L-lactide (PLLA) by the electrospinning technique. Nanofibers with diameters ranging from 50 to 300 nm were obtained. Nanofibers containing up to 35 wt % magnetite nanoparticles displayed superparamagnetism at room temperature. The blocking temperature was about 50 K for an applied field of 500 Oe, and the saturation magnetization was 3.5 emu g(-1) and 1.1 emu g(-1) for Fe3O4/PHEMA and Fe3O4/PLLA nanofibers, respectively, and depended on the amount of Fe3O4 nanoparticles in the nanocomposites. To test such magnetic nano-objects for applications as drug carriers and drug-release systems we incorporated a fluorescent albumin with dog fluorescein isothiocyanate (ADFI).     

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H₂O₂. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.     

Synthesis and characterization of magnetic nanoparticles

Magnetic nanoparticles with average diameter in the range of 6.4-8.3 nni have been synthesized by a chemical co-precipitation of Fe(Ⅱ)and Fe(Ⅲ)salts in 1.5 M NH4OH solution.The size of the magnetic particles is dependent on both temperature and the ionic strength of the iron ion solutions.The magnetic particles formed at higher temperature or lower ionic strength were slightly larger than those formed at lower temperature or higher ionic strength respectively.In spite of the different reaction conditions,all the resultant nanoparticles are nearly spherical and have a similar crystalline structure.At 300 K,such prepared nanoparticles are superparam-agnetic.The saturation magnetizations for 7.8 and 6.4 nm particles are 71 and 63 emu/g respectively,which are only ~ 20-30% less than the saturation magnetization(90 emu/g)of bulk Fe3O4 Our results indicated that a control of the reaction conditions could be used to tailor the size of magnetic nanoparticles in free precipitation.     

Synthesis and characterization of thermosensitive PNIPAM microgels covered with superparamagnetic gamma-Fe2O3 nanoparticles

In the present study we report a facile and reproducible method of preparing magnetic thermosensitive hybrid material based on P(NIPAM) microgels covered with gamma-Fe2O3 nanoparticles of 6-nm size. The iron oxide nanoparticles provided magnetic response to the microgels. In addition, the presence of the magnetic nanoparticles on the microgels altered their swelling behavior and shifted their volume phase transition temperature to higher values. In particular, for inorganic shells with 18% (w/w) of magnetic nanoparticles the volume phase transition of the microgels was shifted from 36 to 40 degrees C. In contrast, for shells consisting of 38% (w/w) magnetic nanoparticles the volume phase transition of the microgels was almost blocked, thus indicating that the microgel thermal response was strongly affected by the presence of the inorganic nanoparticles. The synthesized thermosensitive magnetic microgels are envisaged to be ideal for potential applications as thermosensitive targeted drug delivery systems.     

超顺磁/荧光双功能纳米粒子的合成、表征和生物功能化

通过反相微乳液聚合, 在热解法合成的MnFe2O4纳米粒子表面修饰了一层掺杂有荧光染料(联吡啶钌)的SiO2, 制备了同时具有超顺磁性和荧光特性的双功能纳米粒子. 再通过氨基硅烷的修饰作用, 将该双功能纳米粒子与万古霉素结合, 所得到的生物功能化的纳米粒子表现出很好的对大肠杆菌的识别和磁性分离能力. 本研究制备的超顺磁/荧光双功能纳米粒子具有磁性强、光稳定性高、制备简单、分散性好和尺寸均匀等优点, 可以推断这种新型纳米粒子在生物学、医学和分析化学等领域中将有广阔的应用前景.     

Two step hydrothermal synthesis of flowerbud-like magnetite/graphene oxide hybrid with high-performance microwave absorption

A novel flowerbud-like magnetite/graphene oxide (GO) hybrid was synthesized from facile two-step hydrothermal process by using FeCl₃ as iron source, ethylene glycol as the reducing agent, and graphene oxide as template. The magnetite nanoparticles with the diameters of 70–80 nm were attached onto the surface of graphene oxide through the two-step self-assembly process which enhanced the magnetic properties of the hybrids. The final flowerbud-like magnetite/graphene oxide hybrid emerged with the saturated magnetization of ~84.5 emu g^–1. More importantly, owing to the combined contribution of enhanced dielectric and magnetic properties, the maximum microwave absorption of as-prepared magnetite/GO hybrid reached 30 dB with a thickness of 4 mm. Besides, the absorption bandwidth with a reflection loss above 23 dB ranged from 6.0 to 11.5 GHz.     

Decoration of superparamagnetic iron oxide nanoparticles with Ni2+: agent to bind and separate histidine-tagged proteins

The decoration of iron oxide nanoparticles with Ni2+ ions provided the superparamagnetic nanoparticles with a binding site for His-tagged proteins, allowing their selective binding and convenient separation from a multi-component solution with an appropriately applied magnetic field.     

Cell compatible trimethoprim-decorated iron oxide nanoparticles bind dihydrofolate reductase for magnetically modulating focal adhesion of mammalian cells

On the basis of the high affinity binding of trimethoprim (TMP) to Escherichia coli dihydrofolate reductase (eDHFR), TMP-decorated iron oxide nanoparticles bind to eDHFR with high affinity and specificity, which allows magnetic modulation of focal adhesion of mammalian cells adhered to a surface. Besides being the first example of nanoparticles that selectively bind to eDHFR, the biocompatibility of the conjugate of TMP-iron oxide nanoparticles renders a convenient and versatile platform for investigating the cellular responses to specific, mechanical perturbation of proteins via a magnetic force.     

Decoration of carbon nanotubes with iron oxide

A magnetic composite of multiwalls carbon nanotubes (MWNTs) decorated with iron oxide nanoparticles was synthesized successfully by a simple and effective chemistry precipitation method. The composite was characterized by X-ray diffraction analysis (XRD), Mössbauer spectrum (MS), transmission electron microscopy (TEM), and Fourier transform spectroscopy (FTIR) techniques. The patterns of XRD and MS indicated that MWNTs, γ-Fe₂O₃, and Fe₃O₄ coexisted in the composite. The TEM observation indicated that the nanoparticles of iron oxide were attached on the surface of the MWNTs, and the sizes of the particles ranged from 25 to 80 nm. FTIR spectra showed that SO₄⁻ functional groups existed on the surface of MWNTs after modification by sodium dodecylbenzene sulfonic acid (SDBS), which could immobilize Fe³⁺ ions onto the MWNTs. The hysteresis loops of the MWNTs and decorated MWNTs were measured by vibrating sample magnetometer (VSM), and the results showed that the composite was ferromagnetism with the saturated magnetization of 20.07 emu/g, and the coercive of 163.44 Oe.     

Magnetic manipulation and optical imaging of an active plasmonic single-particle Fe-Au nanorod

Superparamagnetic microbeads play an important role in a number of scientific and biotechnology applications including single-molecule force measurements, affinity separation, and in vivo and in vitro diagnostics. Magneto-optically active nanorods composed of single-crystalline Au and polycrystalline Fe segments were synthesized with diameters of 60 or 295 nm using templated electrodeposition. The Fe section was magnetically soft and had a saturation magnetization of approximately 200 emu/g, resulting in a 10-fold increase in magnetization relative to that iron oxide nanoparticles. The strong plasmonic response of the Au segment of the rod in both the longitudinal and transverse directions made it possible to detect the orientation of a single rod in a polarized light microscope with nanometer resolution. These nanorods provide significantly improved physical properties over iron oxide superparamagnetic beads, making it possible to simultaneously manipulate and monitor the orientation of biomolecules with well-defined forces at the nanometer scale.