Effect of magnetic nanoparticles on magnetic field homogeneity

The mechanism of magnetic nanoparticles(MNPs)affecting magnetic field uniformity is studied in this work.The spatial distribution of MNPs in liquid is simulated based on Monte Carlo method.The induced field of the single MNP is combined with the magnetic field distribution of magnetofluid.In the simulation,magnetic field uniformity is described by a statistical distribution.As the chemical shift(CS)and full width at half maximum(FWHM)of magnetic resonance(MR)spectrum can reflect the uniformity of magnetic field,the simulation is verified by spectrum experiment.Simulation and measurement results prove that the CS and FWHM of the MR spectrum are basically positively correlated with the concentration of MNPs and negatively correlated with the temperature.The research results can explain how MNPs play a role in MR by affecting the uniform magnetic field,which is of great significance in improving the temperature measurement accuracy of magnetic nanothermometers and the spatial resolution of magnetic particle imaging.

Chemiluminescence enzyme immunoassay based on magnetic nanoparticles for detection of hepatocellular carcinoma marker glypican-3

Glypican-3 （GPC3） is reported as a great promising tumor marker for hepatocellular carcinoma （HCC） diagnosis. Highly sensitive and accurate analysis of serum GPC3 （sGPC3）, in combination with or instead of traditional HCC marker alpha-fetoprotein （AFP）, is essential for early diagnosis of I-ICC. Biomaterial-functionalized magnetic particles have been utilized as solid supports with good biological compatibility for sensitive immunoassay. Here, the magnetic nanoparticles （MnPs） and magnetic microparticles （MmPs） with carboxyl groups were further modified with streptavidin, and applied for the development of chemiluminescence enzyme immunoassay （CLEIA）. After comparing between MnPs- and MmPs-based CLEIA, MnPs-based CLEIA was proved to be a better method with less assay time, greater sensitivity, better linearity and longer chemiluminescence platform. MnPs-based CLEIA was applied for detection of sGPC3 in normal liver, hepatocirrhosis, secondary liver cancer and HCC serum samples. The results indicated that sGPC3 was effective in diagnosis of HCC with high performance.

PREPARATION AND CHARACTERIZATION OF PVA COATED MAGNETIC NANOPARTICLES

Polyvinyl alcohol coated magnetic particles (PVA ferrofluids) have been synthesized by chemical co-precipitation of Fe(II)/Fe(III) salts in 1.5 mol/L NH4OH solution at 70 degreesC in the presence of PVA. The resultant colloidal particles have core-shell structures, in which the iron oxide crystallites form the cores and PVA chains form the shells. The hydrodynamic diameter of the colloidal particles is in the range of 108 to 155 nm, which increases with increasing PVA concentration from 5 wt% to 20 wt%, The size of the magnetic cores is ca. 5-10 nm, which is relatively independent of PVA concentration. Under transmission electron microscopic (TEM) examination, the magnetic cores exhibit somewhat irregular shapes varying from spherical, oval, to cubic. Magnetometry measurement revealed that the PVA coated magnetic particles are superparamagnetic. The saturation magnetization of 5 wt% and 20 wt% PVA ferrofluids at 300 K is 54 and 49 emu/g, respectively. All the PVA ferrofluids exhibited excellent colloidal stability in pure water and phosphate buffer saline (PBS, pH = 7.4). The ferrofluids can remain stable in above solutions for more than three months at 4 degreesC.

Simulation research on effect of magnetic nanoparticles on physical process of magneto–acoustic tomography with magnetic induction

Magneto–acoustic tomography with magnetic induction（MAT-MI） is a multiphysics coupled imaging technique that is combined with electrical impedance tomography and ultrasound imaging. In order to study the influence of adding magnetic nanoparticles as a contrast agent for MAT-MI on its physical process, firstly, we analyze and compare the electromagnetic and acoustical properties of MAT-MI theoretically before and after adding magnetic nanoparticles, and then construct a two-dimensional（2 D） planar model. Under the guidance of space-time separation theory, we determine the reasonable simulation conditions and solve the electromagnetic field and sound field physical processes in the two modes by using the finite element method. The magnetic flux density, sound pressure distribution, and related one-dimensional（1 D）, 2 D, and three-dimensional（3 D） images are obtained. Finally, we make a qualitative and quantitative analysis based on the theoretical and simulation results. The research results show that the peak time of the time item separated from the sound source has a corresponding relationship with the peak time of the sound pressure signal. At this moment, MAMPTMI produces larger sound pressure signals, and the sound pressure distribution of the MAMPT-MI is more uniform, which facilitates the detection and completion of sound source reconstruction. The research results may lay the foundation for the MAT-MI of magnetically responsive nanoparticle in subsequent experiments and even clinical applications.

Combined Effects of 50 Hz Magnetic Field and Magnetic Nanoparticles on the Proliferation and Apoptosis of PC12 Cells

Objective To investigate the bioeffects of extremely low frequency （ELF） magnetic field （MF） （50 Hz, 400 μT） and magnetic nanoparticles （MNPs） via cytotoxicity and apoptosis assays on PC12 cells. Methods MNPs modified by SiO2 （MNP-SiO2） were characterized by transmission electron microscopy （TEM）, dynamic light scattering and hysteresis loop measurement. PC12 cells were administrated with MNP-SiO2 with or without MF exposure for 48 h. Cytotoxicity and apoptosis were evaluated with MTI- assay and annexin V-FITC/PI staining, respectively. The morphology and uptake of MNP-SiO2 were determined by TEM. MF simulation was performed by Ansoft Maxwell based on the finite element method. Results MNP-SiO2 were identified as -20 nm （diameter） ferromagnetic particles. MNP-SiO2 reduced cell viability in a dose-dependent manner. MF also reduced cell viability with increasing concentrations of MNP-SiO2. MNP-SiO2 alone did not cause apoptosis in PC12 cells; instead, the proportion of apoptotic cells increased significantly under MF exposure and increasing doses of MNP-SiO2. MNP-SiO2 could be ingested and then cause a slight change in cell morphology. Conclusion Combined exposure of MF and MNP-SiO2 resulted in remarkable cytotoxicity and increased apoptosis in PC12 cells. The results suggested that MF exposure could strengthen the MF of MNPs, which may enhance the bioeffects of ELF MF.

Surface modification of magnetic nanoparticles in biomedicine

Progress in surface modification of magnetic nanoparticles（MNPs） is summarized with regard to organic molecules,macromolecules and inorganic materials. Many researchers are now devoted to synthesizing new types of multi-functional MNPs, which show great application potential in both diagnosis and treatment of disease. By employing an ever-greater variety of surface modification techniques, MNPs can satisfy more and more of the demands of medical practice in areas like magnetic resonance imaging（MRI）, fluorescent marking, cell targeting, and drug delivery.

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.

Multifunctional magnetic nanoparticles for magnetic resonance image-guided photothermal therapy for cancer

Key advances in multifunctional magnetic nanoparticles （MNPs） for magnetic resonance （MR） image-guided pho- tothermal therapy of cancer are reviewed. We briefly outline the design and fabrication of such multifunctional MNPs. Bimodal image-guided photothermal therapies （MR/fluorescence and MR/ultrasound） are also discussed.

A magnetic nanoparticles-based method for DNA extraction from the saliva of stroke patients

C677T polymorphism in the methylenetetrahydrofolate reductase （MTHFR） gene is a risk factor for stroke, suggesting that widespread detection could help to prevent stroke. DNA from 70 stroke pa- tients and 70 healthy controls was extracted from saliva using a magnetic nanoparticles-based method and from blood using conventional methods. Real-time PCR results revealed that the C677T polymorphism was genotyped by PCR using DNA extracted from both saliva and blood samples. The genotype results were confirmed by gene sequencing, and results for saliva and blood samples were consistent. The mutation TT genotype frequency was significantly higher in the stroke group than in controls. Homocysteine levels were significantly higher than controls in both TT genotype groups. Therefore, this noninvasive magnetic nanoparticles-based method using saliva samples could be used to screen for the MTHFR C677T polymorphism in target populations.

Modification of Fe_3O_4 Magnetic Nanoparticles by L-dopa or Dopamine as an Enzyme Support

Fe3O4 magnetic nanoparticles were prepared by co-precipitation of Fe^2＋ and Fe^3＋ in an ammonia solution, and its size was about 36 nm measured by an atomic force microscope. Fe3O4 magnetic nanoparticles were modified by L-dopa or dopamine using sonication method. The analysis of FTIR clearly indicated the formation of Fe-O-C bond. Direct immobilization of trypsin （EC： 3.4.21.4） on Fe3O4 magnetic nanoparticles with L-dopa and dopamine spacer was investigated using glutaraldehyde as a coupling agent. No significant changes in the size and magnetic property of the three kinds of magnetic nanoparticles linked with or without trypsin were observed. The existence of the spacer molecule on magnetic nanoparticles could greatly improve the activity and the storage stability of bound trypsin through increasing the flexibility of enzyme and changing the microenvironment on nanoparticles surface compared to the naked magnetic nanoparticles.

Activity estimation in radioimmunotherapy using magnetic nanoparticles

Objective： Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized ~77Lutetium （177Lu）-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging （MRI）. Methods： ^177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods： single photon emission computed tomography （SPECT）, MRI and organ extraction, which were compared with each other. Results： The good results of quality control tests （labeling yield： 61%±2%, mean nanoparticle hydrodynamic size： 41±15 nm, stability in buffer： 86%±5%, stability in blood serum： 80%±3%, immunoreactivity： 80%±2%） indicated that ^177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that ^177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions： Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.

Immobilized laccase on magnetic nanoparticles for enhanced lignin model compounds degradation

As a natural aromatic polymer,lignin has great potential but limited industrial application due to its complex chemical structure.Among strategies for lignin conversion,biodegradation has attracted promising interest recently in term of efficiency,selectivity and mild condition.In order to overcome the issues of poor stability and non-reusability of enzyme in the biodegradation of lignin,this work explored a protocol of immobilized laccase on magnetic nanoparticles(MNPs)with rough surfaces for enhanced lignin model compounds degradation.Scanning electron microscope with energy dispersive spectrometer(SEM-EDS),flourier transformation infrared spectroscopy(FTIR)and thermal gravimetric analysis(TGA)were utilized to characterize the immobilization of laccase.The results showed a maximum activity recovery of 64.7%towards laccase when it was incubated with MNPs and glutaraldehyde(GA)with concentrations of 6 mg·ml^-1and 7.5 mg·ml^-1for 5 h,respectively.The immobilized laccase showed improved thermal stability and pH tolerance compared with free laccase,and remained more than 80%of its initial activity after 20 days of storage at 4℃.In addition,about 40%residual activity of the laccase remained after 8 times cycles.Gas chromatography–mass spectrometry(GC–MS)was utilized to characterize the products of lignin model compound degradation and activation,and the efficiency of immobilized laccase was calculated to be 1–5 times that of free laccase.It was proposed that the synergistic effect between MNPs and laccase displays an important role in the enhancement of stability and activity in lignin model compound biodegradation.

Structural and Magnetic Analyses of Magnetic Nanoparticles Coated with Oleate Molecules

Physical and chemical properties of the magnetic nanoparticles coated with oleate have been investigated by means of transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Mossbauer spectroscopy, superconducting quantum interference device (SQUID) magnetometry, infrared spectra (IR) and the contact angle device. The results show that doped Al ions in Fe3O4 nanoparticles are located on the octahedral sites of the spinel structure. Oleate is coated on the magnetic nanoparticles with two layers by chemical absorbing, the outer layer can be washed away. The wetting of the surface of magnetic nanoparticles coated with monolayer has been changed from hydrophilicity to hydrophobicity, and the nanoparticles can be dispersed very well in some organic solutions.

Immobilization of Chitosanase on Magnetic Nanoparticles: Preparation, Characterization and Properties

Chitosanase could cleaveβ-1,4-linkage of chitosan to produce chitooligosaccharides(COS)with diverse biological activities.However,there are many limitations on the use of free chitosanase in industrial production.Enzyme immobilization is generally considered a valuable strategy in industrial-scale applications.In this study,the chitosanase Csn-BAC from Bacillus sp.MD-5 was immobilized on Fe_(3)O_(4)-SiO_(2) magnetic nanoparticles(MNPs)to enhance its properties,which could be recovered easily from reaction media using magnetic separation.The activities of Csn-BAC immobilized with MNPs(MNPs@Csn-BAC)were de-termined with temperature and pH,and the thermal-and pH-stabilities,respectively.The reusability of the MNPs@Csn-BAC was determined in repeated reaction cycles.Immobilization enhanced the thermal and pH stability of Csn-BAC compared with the free enzyme.After eight reaction cycles using MNPs@Csn-BAC,the residual enzyme activity was 72.15%.Finally,the amount of COS released by MNPs@Csn-BAC was 1.86 times higher than that of the free Csn-BAC in the catalytic performance experiment.The immobilized Csn-BAC exhibits broad application prospects in the production of COS.

Composite magnetic nanoparticles:Synthesis and cancer-related applications

Recent advances in the preparation and applications of composite magnetic nanoparticles are reviewed and summa- rized, with a focus on cancer-related applications.

Laccase immobilized on magnetic nanoparticles by dopamine polymerization for 4-chlorophenol removal

In this work, a new immobilization method based on dopamine(DA) self-polymerization was developed for laccase immobilization on magnetic nanoparticles(Fe_3O_4 NPs). To optimize the immobilization condition including reaction pH, DA concentration and enzyme concentration, a central composite response surface method was applied. The optimal condition was determined as p H value of 5.92, laccase concentration of 0.25 mg mL^(-1) and DA concentration of 12.74 mg mL^(-1), under which a high enzyme activity recovery of 88.17% was obtained.By comparing with free laccase, the stabilities of immobilized laccase towards p H, thermostability, storage were enhanced significantly.Approximately 60% of relative activity for immobilized laccase was remained after being incubated for 6 h at 50℃, but the free laccase only remained 25%. After 40 days of storage at 4℃, the laccase immobilized by DA kept about 89% of its original activity, but the free laccase only retained 48%. After recycled 10 times, the relative activity of immobilized laccase still retained 70%. The immobilized laccase was then applied to catalyze the degradation of 4-chlorophenol(4-CP), 86% percentage of 4-CP was removed within 2 h. After degraded 10 times, the relative activity of immobilized laccase still remained 64% of its initial activity, which exhibits an excellent reusability and operational stability.

Magnetic nanoparticle-based cancer therapy

Nanoparticles（NPs） with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles（MNPs） that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging（MRI） monitoring cancer therapy and magnetic tissue engineering are also addressed.

Magnetic Particle Imaging for Magnetic Hyperthermia Treatment: Visualization and Quantification of the Intratumoral Distribution and Temporal Change of Magnetic Nanoparticles in Vivo

Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.

Study on Tat Mediated Magnetic Nanoparticles Having Composite Targeting Function

This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as a drug carrier, Methotrexate (MTX) was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75 nm were prepared and characterized by TEM, AFM and VSM.The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity.

Magnetic nanoparticle-based cancer nanodiagnostics

Diagnosis facilitates the discovery of an impending disease. A complete and accurate treatment of cancer depends heavily on its early medical diagnosis. Cancer, one of the most fatal diseases world-wide, consistently affects a larger number of patients each year. Magnetism, a physical property arising from the motion of electrical charges, which causes attraction and repulsion between objects and does not involve radiation, has been under intense investigation for several years. Magnetic materials show great promise in the application of image contrast enhancement to accurately image and diagnose cancer. Chelating gadolinium （Gd Ⅲ） and magnetic nanoparticles （MNPs） have the prospect to pave the way for diagnosis, operative management, and adjuvant therapy of different kinds of cancers. The potential of MNP-based magnetic resonance （MR） contrast agents （CAs） now makes it possible to image portions of a tumor in parts of the body that would be unclear with the conventional magnetic resonance imaging （MRI）. Multiple functionalities like variety of targeting ligands and image contrast enhancement have recently been added to the MNPs. Keeping aside the additional complexities in synthetic steps, costs, more convoluted behavior, and effects in-vivo, multifunctional MNPs still face great regulatory hurdles before clinical availability for cancer patients. The trade-off between additional functionality and complexity is a subject of ongoing debate. The recent progress regarding the types, design, synthesis, morphology, characterization, modification, and the in-vivo and in-vitro uses of different MRI contrast agents, including MNPs, to diagnose cancer will be the focus of this review. As our knowledge of MNPs＇ characteristics and applications expands, their role in the future management of cancer patients will become very important. Current hurdles are also discussed, along with future prospects of MNPs as the savior of cancer victims.