The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells

One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe₂O₃) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe₂O₃ in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe₂O₃ on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe₂O₃). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe₂O₃ exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe₂O₃ exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe₂O₃ (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe₂O₃ have some cytotoxicity that may cause side effects on normal endothelial cells.     

Research progress on magnetic nanoparticles for magnetic induction hyperthermia of malignant tumor

As a new malignant tumor therapy method with low side effect, high safety and efficiency, magnetic induction hyperthermia (MIH) has attracted great attention in recent years. As magnetic induction heating media, magnetic nanoparticles (MNPs) are critical for the development of MIH. For clinical safety, the MNPs need a high heating efficiency to reduce the applied dose, minimizing the risk of side effect. Increasing the saturation magnetization and initial susceptibility, adjusting the magnetocrystalline anisotropy constant and particle size to the optimal values are the effective methods of improving heating efficiency. On the other hand, a suitable Curie temperature is desired to realize the self-regulation of the therapy temperature, avoiding the use of clumsy and expensive temperature monitoring and control devices. Substituting the magnetic ions in tetrahedral (A) site of the spinel ferrite with nonmagnetic ions or magnetic ions with smaller magnetic moments can effectively reduce the superexchange interaction between the A and B (octahedral) sites, decreasing Curie temperature. Yet, the reduction of the Curie temperature by ion doping usually reduces the saturation magnetization, decreasing heating efficiency. Increasing the fraction of heat generated by relaxation loss and increasing the saturation magnetization may be used to improve the heating efficiency.     

Mass‐transfer enhancement in single drop extraction in the presence of magnetic nanoparticles and magnetic field

Magnetite nanoparticles with an average particle size of 28.8 nm were synthesized, coated with oleic acid, and characterized using various techniques such as DLS, FT‐IR, SEM, XRD, VSM, and UV‐Vis analysis. A nanofluid consisting of synthesized nanoparticles and 5 wt % acetic acid in toluene as the dispersed phase was prepared and used in the chemical test system, Toluene‐Acetic Acid‐Water, for the single drop extraction in the presence and absence of an external oscillating magnetic field. Influences of various operating and design parameters such as nanoparticle concentration, drop diameter, and the applied current and frequency on the overall mass‐transfer coefficients for the mass‐transfer direction from d→c were investigated carefully. The obtained results were used to propose a general correlation for the mass‐transfer enhancement. It was found that the maximum mass‐transfer enhancement compared with that obtained in the absence of nanoparticles and the oscillating magnetic field is about 259%. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4466–4479, 2016     

The effect of two novel amino acid-coated magnetic nanoparticles on survival in vascular endothelial cells,bone marrow stromal cells,and macrophages

Magnetic nanoparticles (MNPs) have been popularly used in many fields. Recently, many kinds of MNPs are modified as new absorbents, which have attracted considerable attention and are promising to be applied in waste water. In our previous study, we synthesized two novel MNPs surface-coated with glycine or lysine, which could efficiently remove many anionic and cationic dyes under severe conditions. It should be considered that MNP residues in water may exert some side effects on human health. In the present study, we evaluated the potential nanotoxicity of MNPs in human endothelial cells, macrophages, and rat bone marrow stromal cells. The results showed that the two kinds of nanoparticles were consistently absorbed into the cell cytoplasm. The concentration of MNPs@Gly that could distinctly decrease survival was 15 μg/ml in human umbilical vascular endothelial cells (HUVECs) or bone marrow stromal cells (BMSCs) and 10 μg/ml in macrophages. While the concentration of MNPs@Lys that obviously reduced viability was 15 μg/ml in HUVECs or macrophages and 50 μg/ml in BMSCs. Furthermore, cell nucleus staining and cell integrity assay indicated that the nanoparticles induced cell apoptosis, but not necrosis even at a high concentration. Altogether, these data suggest that the amino acid-coated magnetic nanoparticles exert relatively high cytotoxicity. By contrast, lysine-coated magnetic nanoparticles are more secure than glycine-coated magnetic nanoparticles.     

Synthesis of hollow maghemite (-Fe2O3) particles for magnetic field and pH-responsive drug delivery and lung cancer treatment

The development of smart stimuli-responsive materials for drug delivery offers new opportunities for precise drug release and cancer chemotherapy. A combination of more than one stimuli is highly desirable to further maximize the therapy by taking the advantages of various unique merits. Herein, we employed polyethylene glycol (PEG) functionalized γ-Fe₂O₃ particles (γ-Fe₂O₃/PEG) as a novel magnetic drug carrier for doxorubicin (DOX) delivery. The results showed that the γ-Fe₂O₃/PEG exhibited excellent thermal effects under alternating magnetic field (AMF), high magneto-thermal stability, and large DOX loading capacity. Furthermore, the effects of pH and AMF on the DOX drug release were studied. It was discovered that DOX loaded γ-Fe₂O₃/PEG carriers were highly responsive to both AMF and pH, resulting in significantly improved cancer cell killing capability over a single stimulus. The magnetic and pH responsive drug delivery system provided a new opportunity to minimize the side effects and maximize the therapeutic efficiency of lung cancer treatment.     

Magnetic-field assisted mixing of liquids using magnetic nanoparticles

Size and magnetic properties of magnetic nanoparticles (MNPs) in fluids allow special remote control of fluid flow using appropriate externally applied magnetic fields, especially when submicronic mixing is critical, inter alia, for catalytic reactions, separation and drug delivery. This work explores MNPs as nanoscale devices to control mixing at microscale by submitting the system of interest to a rotating magnetic field (RMF). Magnetic nanoparticles are harnessed by RMF and converted into nanostirrers thereby generating MNP-pinned localized agitation in the liquid phase. Using this technique, self-diffusion coefficient of water in a static diffusion cell was intensified up to 200 folds. Also, axial dispersion of capillary Poiseuille flows under RMF underwent a reduction prompted by MNP-mediated intensification of lateral mixing relative to that in absence of magnetic field. Finally a multiphase flow case concerned gas–liquid mass transfer from oxygen Taylor bubbles to the liquid in capillaries where dilute MNP solutions led to measurable enhancement of k_La under RMF.     

Therapeutic effect of magnetic nanoparticles on calcium silicate bioceramic in alternating field for biomedical application

The cancerous bone may be treated using magnetite nanoparticles (MNPs) coupled with hyperthermia treatment technology. During the last three decades, calcium-silicate (CS) based bioceramics have been investigated as a proper choice due to their bioactivity, biocompatibility, magnetization property, and ability to form suitable apatite for hard tissue engineering approaches. For this purpose, three-dimensional bio-nanocomposite scaffolds utilizing bioactive wollastonite (WS) and bioglass (BG) as composed based materials with 0 wt% (S1), 5 wt% (S2), 10 wt% (S3), and 15 wt% (S4) of Zr–Fe₃O₄ are considered in this study. These materials with two various space-agents such as sodium chloride (NaCl) and sodium bicarbonate (NaHCO₃) particles containing ball mill with high energy and pressing under 150 MPa, and sintered at 850 °C are analyzed. Additionally, X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating-sample magnetometer (VSM), and mechanical tests include of toughness and compressive strength are investigated. The powder's and scaffold's crystals size are measured between 30 and 50 nm, and the pores and porosity size are measured from 70 to 180 μm and 25%–40%. The VSM curves illustrate that the zirconium-ferrite has a soft magnetic property, which is easily magnetized by applying a small amount of magnetic field, and it rapidly loses its magnetic moment by cutting off the field. The low coercive force, as well as high magnetic saturation with low residue, are represented for the S2 and S3. The obtained outcomes indicate that the best amounts of mechanical properties amongst the specimens are related to the specimen with 15 wt%, 7.9 ± 1 MPa of compressive strength, and 203.3 ± 10 MPa of elastic modulus. Likewise, the biological assessment shows that the sample containing 10 wt% MNPs provides a better apatite creation on porous scaffolds after 28 days. The gained outcomes represent that those specimens containing 10 and 15 wt% MNPs provide proper biological and mechanical replies.     

External magnetic field-induced selective biodistribution of magnetoliposomes in mice

ABSTRACT: This study looked at the effect of an external magnet on the biodistribution of magnetoliposomes intravenously administrated in mice (8 mg iron/kg) with and without induced acute inflammation. Our results showed that due to enhanced vascular permeability, magnetoliposomes accumulated at the site of inflammation in the absence of an external magnetic field, but the amount of iron present increased under the effect of a magnet located at the inflammation zone. This increase was dependent on the time (20 or 60 min) of exposure of the external magnetic field. It was also observed that the presence of the magnet was associated with lower amounts of iron in the liver, spleen, and plasma than was found in mice in which a magnet had not been applied. The results of this study confirm that it is possible to target drugs encapsulated in magnetic particles by means of an external magnet.     

Influence of structure of iron nanoparticles in aggregates on their magnetic properties

Zero-valent iron nanoparticles rapidly aggregate. One of the reasons is magnetic forces among the nanoparticles. Magnetic field around particles is caused by composition of the particles. Their core is formed from zero-valent iron, and shell is a layer of magnetite. The magnetic forces contribute to attractive forces among the nanoparticles and that leads to increasing of aggregation of the nanoparticles. This effect is undesirable for decreasing of remediation properties of iron particles and limited transport possibilities. The aggregation of iron nanoparticles was established for consequent processes: Brownian motion, sedimentation, velocity gradient of fluid around particles and electrostatic forces. In our previous work, an introduction of influence of magnetic forces among particles on the aggregation was presented. These forces have significant impact on the rate of aggregation. In this article, a numerical computation of magnetic forces between an aggregate and a nanoparticle and between two aggregates is shown. It is done for random position of nanoparticles in an aggregate and random or arranged directions of magnetic polarizations and for structured aggregates with arranged vectors of polarizations. Statistical computation by Monte Carlo is done, and range of dominant area of magnetic forces around particles is assessed.     

Magnetically stabilized fluidization of a mixture of magnetic and non-magnetic particles in a transverse magnetic field

This paper presents an investigation of the hydrodynamic behavior of a gas-solid magnetically stabilized fluidized bed. It consists of a mixture of spherical steel particles with glass balls subjected to a magnetic field, transverse to the gas flow, which is created by two permanent magnets. Pressure drop, bed stability and expansion are studied. A data correlation in good agreement with experimental results was developed. It takes into account the modification of the bed structure in the presence of two types of particles: steel particles forming chains following the field lines and considered as “pseudo-plate” particles and non-aggregated non-magnetic particles.     

Cytotoxic effects and the mechanism of three types of magnetic nanoparticles on human hepatoma BEL-7402 cells

The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe₃O₄, oleic acid-coated Fe₃O₄ (OA-Fe₃O₄), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe₃O₄ and OA-Fe₃O₄) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe₃O₄ > OA-Fe₃O₄.     

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.     

Rapid and large‐scale separation of magnetic nanoparticles by low‐field permanent magnet with gas assistance

Bubbles can be used to greatly improve the speed of magnetic separation (MS) and overcome the limitation of magnetic force on the capture distance, making low‐field MS highly efficient and easily scalable. This novel method leads to the development of a medium‐free continuous gas‐assisted magnetic separator on small pilot scale using low‐field permanent magnet. This separator is demonstrated highly efficient for recovery of proteins‐loaded magnetic nanoparticles from large volume biosuspension. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3101–3106, 2014     

Study on performance of magnetic fluorescent nanoparticles as gene carrier and location in pig kidney cells

We evaluated the performance of green fluorescent magnetic Fe₃O₄ nanoparticles (NPs) as gene carrier and location in pig kidney cells. When the mass ratio of NPs to green fluorescent protein plasmid DNA reached 1:16 or above, DNA molecules can be combined completely with NPs, which indicates that the NPs have good ability to bind negative DNA. Atomic force microscopy (AFM) experiments were carried out to investigate the binding mechanism between NPs and DNA. AFM images show that individual DNA strands come off of larger pieces of netlike agglomerations and several spherical nanoparticles are attached to each individual DNA strand and interact with each other. The pig kidney cells were labelled with membrane-specific red fluorescent dye 1,1^′-dioctadecyl-3,3,3^′,3^′-tetramethylindocarbocyanine perchlorate and nucleus-specific blue fluorescent dye 4^′,6-diamidino-2-phenylindole dihydrochloride. We found that green fluorescent nanoparticles can past the cell membrane and spread throughout the interior of the cell. The NPs seem to locate more frequently in the cytoplasm than in the nucleus.     

Electrosynthesis of Co,Ni and Zn ferrites nanoparticles in the presence of external magnetic field

Magnetic complex oxides of iron nanoparticles are among the most important materials that have been studied. They have been widely used in different areas such as electronic devices, information storage, biomedical areas, drug-delivery, catalyst, and wastewater treatment. In different applications of nanoparticles, the shape and size of particles are very important because the electrical, optical, and magnetic properties of the nanoparticles depend on their dimension. In this study, nanoparticles of cobalt, nickel, and zinc ferrites were synthesized in uniform size by an electrochemical technique. First, the anode was made electrochemically by depositing each metal of zinc, nickel, and cobalt on the iron sheet from the solutions of 0.1 M Co²⁺, Ni²⁺, and Zn²⁺ ions as the precursor. Then the electrosynthesis of ferrite nanoparticles was performed in a second electrochemical cell where the prepared electrode was anode and stainless steel (316L) was cathode in the electrolyte solution of CTAB 0.04 M. The optimized value of current density was applied to the electrochemical cell. After then the same synthesis was carried out in the magnetic field supplied by two magnets. The prepared nanoparticles were characterized by x-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were investigated by vibrating sample magnetometer (VSM). The comparison of two samples prepared in the magnetic field and without it showed the average size of the samples synthesized in the magnetic field was in the narrower size distribution of 20–30 nm and the saturation magnetization of the nanoparticles increased in the magnetic field.     

Synthesis and magneto-structural properties of chitosan coated ultrafine cobalt ferrite nanoparticles for magnetic fluid hyperthermia in viscous medium

AC induction heating mediated magnetic fluid hyperthermia of superparamagnetic nanoparticles (MNPs) is being widely explored for localized thermo-therapy of tumours. One of the primary hindrances for rapid adaptation of this technique is the loss of heating efficiency when the MNPs are placed within the viscous tissue medium, which necessitates undesired increase in MNP concentrations or exposure time during practical applications. With an objective to mitigate this, here we report the viscosity independent magnetic hyperthermia properties of biocompatible ultrafine (average size ～ 2.5 nm) chitosan-coated superparamagnetic CoFe₂O₄ MNPs synthesized using a low-cost co-precipitation technique. The presence of the chitosan coating is confirmed from Fourier transform infrared and X-ray photoelectron spectroscopy. The superparamagnetic nature of the synthesized MNPs at 300 K is confirmed from Mössbauer spectroscopy, isothermal and temperature dependent magnetization studies. Experimental findings indicate a higher field-induced heating efficiency for the chitosan-coated MNPs due to superior colloidal stability. The ultrafine size, combined with higher anisotropy energy density, results in viscosity independent Nèel relaxation-dominated magneto-thermal energy conversion for the CoFe₂O₄ MNPs. Experimental results reveal negligible loss of heating efficiency due to partial abrogation of Brownian relaxation when the chitosan-coated MNPs are immobilized in a tissue-equivalent agar medium, which is beneficial for practical applications. The heating efficiency of ～72.1 ± 2.8 W/g_Fe (at 33.1 kA/m and 126 kHz), obtained in the present study for the chitosan-coated MNPs, is higher than the previously documented values for ultrafine CoFe₂O₄ MNPs, which is useful for reducing the exposure time during practical applications. Further, the chitosan coating rendered the ultrafine CoFe₂O₄ MNPs bio-compatible against L929 cell line. The satisfactory magnetic fluid hyperthermia efficiency, negligible room temperature coercivity, retention of the field-induced heating efficiency in tissue-equivalent agar medium due to Nèel-dominated relaxation dynamics and superior biocompatibility, make the chitosan-coated ultrafine CoFe₂O₄ MNPs an attractive candidate for practical MFH applications.     

The heating effect of iron-cobalt magnetic nanofluids in an alternating magnetic field: application in magnetic hyperthermia treatment

In this research, FeCo alloy magnetic nanofluids were prepared by reducing iron(III) chloride hexahydrate and cobalt(II) sulfate heptahydrate with sodium borohydride in a water/CTAB/hexanol reverse micelle system for application in magnetic hyperthermia treatment. X-ray diffraction, electron microscopy, selected area electron diffraction, and energy-dispersive analysis indicate the formation of bcc-structured iron-cobalt alloy. Magnetic property assessment of nanoparticles reveals that some samples are single-domain superparamagnetic, while others are single- or multi-domain ferromagnetic. The stability of the magnetic fluids was achieved by using a CTAB/1-butanol surfactant bilayer. Results of Gouy magnetic susceptibility balance experiments indicate good stability of FeCo nanoparticles even after dilution. The inductive properties of corresponding magnetic fluids including temperature rise and specific absorption rate were determined. Results show that with increasing of the nanoparticle size in the single-domain size regime, the generated heat increases, indicating the significant effect of the hysteresis loss. Finally, the central parameter controlling the specific absorption rate of nanoparticles was introduced, the experimental results were compared with those of the Stoner-Wohlfarth model and linear response theory, and the best sample for magnetic hyperthermia treatment was specified.     

Structural properties of magnetic nanoparticles determine their heating behavior - an estimation of the in vivo heating potential

Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimally invasive tool for localized tumor treatment by sensitizing or killing tumor cells with the help of thermal stress. Therefore, the selection of MNP exhibiting a sufficient heating capacity (specific absorption rate, SAR) to achieve satisfactory temperatures in vivo is necessary. Up to now, the SAR of MNP is mainly determined using ferrofluidic suspensions and may distinctly differ from the SAR in vivo due to immobilization of MNP in tissues and cells. The aim of our investigations was to study the correlation between the SAR and the degree of MNP immobilization in dependence of their physicochemical features.In this study, the included MNP exhibited varying physicochemical properties and were either made up of single cores or multicores. Whereas the single core MNP exhibited a core size of approximately 15 nm, the multicore MNP consisted of multiple smaller single cores (5 to 15 nm) with 65 to 175 nm diameter in total. Furthermore, different MNP coatings, including dimercaptosuccinic acid (DMSA), polyacrylic acid (PAA), polyethylenglycol (PEG), and starch, wereinvestigated. SAR values were determined after the suspension of MNP in water. MNP immobilization in tissues was simulated with 1% agarose gels and 10% polyvinyl alcohol (PVA) hydrogels.The highest SAR values were observed in ferrofluidic suspensions, whereas a strong reduction of the SAR after the immobilization of MNP with PVA was found. Generally, PVA embedment led to a higher immobilization of MNP compared to immobilization in agarose gels. The investigated single core MNP exhibited higher SAR values than the multicore MNP of the same core size within the used magnetic field parameters. Multicore MNP manufactured via different synthesis routes (fluidMAG-D, fluidMAG/12-D) showed different SAR although they exhibited comparable core and hydrodynamic sizes. Additionally, no correlation between ζ-potential and SAR values after immobilization was observed.Our data show that immobilization of MNP, independent of their physicochemical properties, can distinctly affect their SAR. Similar processes are supposed to take place in vivo, particularly when MNP are immobilized in cells and tissues. This aspect should be adequately considered when determining the SAR of MNP for magnetic hyperthermia.     

Investigation of the effect of magnetic field on mass transfer parameters of CO2 absorption using Fe3O4‐water nanofluid

In this study, the enhancement of physical absorption of carbon dioxide by Fe₃O₄‐water nanofluid under the influence of AC and DC magnetic fields was investigated. Furthermore, a gas‐liquid mass transfer model for single bubble systems was applied to predict mass transfer parameters. The coated Fe₃O₄ nanoparticles were prepared using co‐percipitation method. The results from characterization indicated that the nanoparticles surfaces were covered with hydroxyl groups and nanoparticles diameter were 10–13 nm. The findings showed that the mass transfer rate and solubility of carbon dioxide in magnetic nanofluid increased with an increase in the magnetic field strength. Results indicated that the enhancement of carbon dioxide solubility and average molar flux gas into liquid phase, particularly in the case of AC magnetic field. Moreover, results demonstrated that mass diffusivity of CO₂ in nanofluid and renewal surface factor increased when the intensity of the field increased and consequently diffusion layer thickness decreased. © 2016 American Institute of Chemical Engineers AIChE J, 63: 2176–2186, 2017