Structural control of magnetic nanoparticles for positive nuclear magnetic resonance imaging

In addition to the tens of millions of medical doses consumed annually around the world,a vast number of nuclear magnetic resonance imaging(MRI)contrast agents are being deployed in MRI research and development,offering precise diagnostic information,targeting capabilities,and analyte sensing.Superparamagnetic iron oxide nanoparticles(SPIONs)are notable among these agents,providing effective and versatile MRI applications while also being heavy-metal-free,bioconjugatable,and theranostic.We designed and implemented a novel two-pronged computational and experimental strategy to meet the demand for the efficient and rigorous development of SPION-based MRI agents.Our MATLAB-based modeling simulation and magnetic characterization revealed that extremely small maghemite SPIONs in the 1-3 nm range possess significantly reduced transversal relaxation rates(R_(2))and are therefore preferred for positive(T_(1)-weighted)MRI.Moreover,X-ray diffraction and X-ray absorption fine structure analyses demonstrated that the diffraction pattern and radial distribution function of our SPIONs matched those of the targeted maghemite crystals.In addition,simulations of the X-ray near-edge structure spectra indicated that our synthesized SPIONs,even at 1 nm,maintained a spherical structure.Furthermore,in vitro and in vivo MRI investigations showed that our 1-nm SPIONs effectively highlighted whole-body blood vessels and major organs in mice and could be cleared through the kidney route to minimize potential post-imaging side effects.Overall,our innovative approach enabled a swift discovery of the desired SPION structure,followed by targeted synthesis,synchrotron radiation spectroscopic studies,and MRI evaluations.The efficient and rigorous development of our high-performance SPIONs can set the stage for a computational and experimental platform for the development of future MRI agents.

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.

Adsorption behavior and adsorption mechanism of Cu(Ⅱ) ions on amino-functionalized magnetic nanoparticles

Amino-functionalized magnetic nanoparticle （NH2-MNP） were prepared by a sol-gel approach. The adsorption behavior of Cu（II） ions on NH2-MNP was discussed systematically by batch experiments. The effects of initial Cu（II） ions concentration, time, pH and temperature were investigated. In kinetic studies, the pseudo-second-order model was successfully employed, and the pseudo-first-order model substantiated that Cu（II） adsorption on NH2-MNP was a diffusion-based process. Langmuir model and Dubinin-Radushkevich model （R2〉0.99） were more corresponded with the adsorption isotherm data of Cu（II） ions than Freundlich model. The adsorption capacity was increased with the increment of temperature and pH. NH2-MNP remains excellent Cu（II） recoveries after reusing five adsorption and desorption cycles, making NH2-MNP a promising candidate for repetitively removing heavy metal ions from environmental water samples. According to the results obtained from adsorption activation energy and thermodynamic studies, it can be inferred that the main adsorption mechanism between absorbent and Cu（II） ions is ion exchange-surface complexation.

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.

Effect of targeted magnetic nanoparticles containing 5-FU on expression of bcl-2, bax and caspase 3 in nude mice with transplanted human liver cancer

AIM: To investigate the anti-tumor effect and mechanisms of magnetic nanoparticles targeting hepatocellular carcinoma. METHODS: Human hepatocellular carcinoma was induced in nude mice, and the mice were randomly divided into group A receiving normal saline, group B receiving magnetic nanoparticles containing 5-fluorouracil (5-FU), group C receiving 5-FU, and group D receiving magnetic nanoparticles containing 5-FU with a magnetic field built in tumor tissues. The tumor volume was measured on the day before treatment and 1, 4, 7, 10 and 13 d after treatment. Tumor tissues were isolated for examination of the expression of bcl-2, bax and caspase 3 by immunohistochemical method, reverse transcription polymerase chain reaction and Western blotting. RESULTS: The tumor volume was markedly lower in groups C and D than in groups A and B (group C or D vs group A or B, P < 0.01). The volume was markedly lower in group D than in group C (P < 0.05). The expression of protein and mRNA of bcl-2 was markedly lower in groups C and D than in groups A and B (group C or D vs group A or B, P < 0.01), and was markedly lower in group D than in group C (P < 0.01). The expression of bax and caspase 3 in groups C and D was signif icantly increased, compared with that in groups A and B (P < 0.01). CONCLUSION: The targeted magnetic nanoparticles containing 5-FU can improve the chemotherapeutic effect of 5-FU against hepatocellular carcinoma by decreasing the expression of bcl-2 gene, and increasing the expression of bax and caspase 3 genes.

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.

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.

Fabrication of Poly（y-glutamic acid）-coated Fe3O4 Magnetic Nanoparticles and Their Application in Heavy Metal Removal

In this study, poly（y-glutamic acid）-coated Fe3O4 magnetic nanoparticles （y-PGA/Fe304 MNPs） were successfully fabricated using the co-precipitation method. Fe3O4 MNPs were also prepared for comparison. The av erage size and specific surface area results reveal that 7-PGA/Fe304 MNPs （52.4 nm, 88.41 m2.g-1） have smaller particle size and larger specific surface area_ than Fe3O4 MNPs （62.0 nm, 76.83 mLg-1）. The y-PGA/Fe3O4 MNPs

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.

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.

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.

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 Penicillin G Acylase on Magnetic Nanoparticles Modified by Ionic Liquids

Functionalized ionic liquids containing ethyoxyl groups were synthesized and immobilized on magnetic silica nanoparticles （MSNP） prepared by two steps, i.e., Fe304 synthesis and silica shell growth on the surface. This magnetic nanoparticle supported ionic liquid （MNP-IL） were applied in the immobilization of penicillin G acylase （PGA）. The MSNPs and MNP-ILs were characterized by themeans of Fourier transform infrared spectroscopy （FTIR）, scanning electron microscopy （SEM）, transmission electron microscopy （TEM）, and vibrating sample magnetometer （VSM）. The results showed that the average size of magnetic Fe304 nanoparticles and MSNPs were -10 and -90 nm, respectively. The saturation magnetizations of magnetic Fe304 nanoparticles and MNP-ILs were 63.7 and 26.9 A＇m2·kg^-1, respectively. The MNP-IL was successfully applied in the immobilization of PGA. The maximum amount of loaded enzyme-was about 209 mg·g^-1 （based on carder）, and the highest enzyme activity of immobilized PGA （based on ImPGA） was 261 U·g^-1. Both the amount of loaded enzyme and the activity of ImPGA are at the same leyel of or higher than that in previous reports. After 10 consecutive operat!ons, ImPGA still mainrained 62% of its initial activity, indicating the＇good recovery property of ImPGA activity. The ionic liquid modified magnetic particles integrate the magnetic properties of Fe304 and the structure-tunable properties of ionic liquids, and have extensive potential uses in protein immobilization and magnetic bioseparation. This work may open up a novel strategy to immobilize proteins by ionic liquids.

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.

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.

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.

Characteristics of non-magnetic nanoparticles in magnetically fluidized bed by adding coarse magnets

The fluidization behavior of SiO2, ZnO and TiO2 non-magnetic nanoparticles was investigated in a magnetically fluidized bed （MFB） by adding coarse magnets. The effects of both the amount of coarse magnets and the magnetic field intensity on the fluidization quality of these nanoparticles were investigated. The results show that the coarse magnets added to the bed lead to a reduction in the size of the aggregates formed naturally by the primary nanopartieles. As the macroscopic performances of improved fluidization quality, the bed expansion ratio increases whilst the minimum fluidization velocity decreases with increasing the magnetic field intensity, but for TiO2 nanoparticles there exists a suitable magnetic field intensity of 0.059 6 T. The optimal amounts of coarse magnets for SiO2, ZnO and TiO2 non-magnetic nanoparticles are 40%, 50% and 60% （mass fraction）, respectively. The bed expansion results analyzed by the Richardson-Zaki scaling law show that the exponents depend on both the amount of coarse magnets and the magnetic field intensity.

Intensification of levofloxacin sono-degradation in a US/H_2O_2 system with Fe_3O_4 magnetic nanoparticles

Fe3O4 magnetic nanoparticles(MNPs) were synthesised, characterised, and used as a peroxidase mimetic to accelerate levofloxacin sono-degradation in an ultrasound(US)/H2O2 system. The Fe3O4 MNPs were in nanometre scale with an average diameter of approximately 12 to 18 nm. The introduction of Fe3O4 MNPs increased levofloxacin sono-degradation in the US/H2O2 system. Experimental parameters, such as Fe3O4 MNP dose, initial solution p H, and H2O2 concentration, were investigated by a one-factor-at-a-time approach. The results showed that Fe3O4 MNPs enhanced levofloxacin removal in the p H range from 4.0 to 9.0. Levofloxacin removal ratio increased with Fe3O4 MNP dose up to 1.0 g·L-1and with H2O2 concentration until reaching the maximum. Moreover, three main intermediate compounds were identified by HPLC with electrospray ionisation tandem mass spectrometry, and a possible degradation pathway was proposed. This study suggests that combination of H2O2, Fe3O4 MNPs and US is a good way to improve the degradation efficiency of antibiotics.