Contrast-enhanced susceptibility weighted imaging with ultrasmall superparamagnetic iron oxide improves the detection of tumor vascularity in a hepatocellular carcinoma nude mouse model.

PURPOSE: To evaluate the effectiveness of contrast-enhanced susceptibility-weighted imaging with ultrasmall superparamagnetic iron oxide (USPIO-enhanced SWI) in the assessment of intratumoral vascularity in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Orthotopic xenograft HCC nude mouse models were established first and magnetic resonance imaging (MRI) examinations were performed on a 1.5T MR scanner 28 days later. Three groups of mice, 10 in each, were imaged using unenhanced and USPIO-enhanced SWI at doses of 4, 8, and 12 mg Fe/kg. Intratumoral susceptibility signal intensity (ITSS) was scored. ITSS-to-tumor contrast-to-noise ratio (ITSST-CNR) was measured. These measurements were compared between unenhanced and USPIO-enhanced SWI at each dose and differences in the measurements between different dose groups were estimated. Correlation between ITSS and tumor microvessel density (MVD) was analyzed. RESULTS: Compared with unenhanced SWI, significantly higher ITSS was identified on USPIO-enhanced SWI at doses of 8 mg Fe/kg (Z = -2.000, P = 0.046) and 12 mg Fe/kg (Z = -2.333, P = 0.020). Significantly higher ITSST-CNR was found on USPIO-enhanced SWI than that on unenhanced SWI (P < 0.05). Significantly higher ITSST-CNR at a dose of 8 mg Fe/kg was observed than that at 4 mg Fe/kg (Z = -3.326, P = 0.001). Positive correlation between ITSS on USPIO-enhanced SWI at a dose of 8 mg Fe/kg and tumor MVD was demonstrated (r = 0.817, P = 0.004). CONCLUSION: USPIO-enhanced SWI at a dose of 8 mg Fe/kg greatly improves the detection of intratumoral vascularity in a xenograft HCC model. J. Magn. Reson. Imaging 2016;44:288-295.

Synthesis and characterization of pore size-tunable magnetic mesoporous silica nanoparticles.

Magnetic mesoporous silica nanoparticles (M-MSNs) are emerging as one of the most appealing candidates for theranostic carriers. Herein, a simple synthesis method of M-MSNs with a single Fe(3)O(4) nanocrystal core and a mesoporous shell with radially aligned pores was elaborated using tetraethyl orthosilicate (TEOS) as silica source, cationic surfactant CTAB as template, and 1,3,5-triisopropylbenzene (TMB)/decane as pore swelling agents. Due to the special localization of TMB during the synthesis process, the pore size was increased with added TMB amount within a limited range, while further employment of TMB lead to severe particle coalescence and not well-developed pore structure. On the other hand, when a proper amount of decane was jointly incorporated with limited amounts of TMB, effective pore expansion of M-MSNs similar to that of analogous mesoporous silica nanoparticles was realized. The resultant M-MSN materials possessed smaller particle size (about 40-70 nm in diameter), tunable pore sizes (3.8-6.1 nm), high surface areas (700-1100 m(2)/g), and large pore volumes (0.44-1.54 cm(3)/g). We also demonstrate their high potential in conventional DNA loading. Maximum loading capacity of salmon sperm DNA (375 mg/g) was obtained by the use of the M-MSN sample with the largest pore size of 6.1 nm.

Hydroxylapatite nanorods: an efficient and promising carrier for gene transfection.

Calcium phosphate (CaP) has been used as the vector for gene transfection in the past three decades with the characteristics of excellent biocompatibility and biodegradability. However, clinical application of calcium phosphate is still not popular due to poor-controlling of DNA/CaP complex preparation and its low transfection efficiency. In this study, block copolymer (PLGA-mPEG) assisted synthesis of hydroxylapatite (HAP) nanorods and DNA post-adsorbing method for transfection in vitro have been reported. By hydrothermal treatment, HAP nanorods with relatively uniform sizes of ~100 nm in length and ~25 nm in diameter and high crystallinity were prepared, which were characterized by TEM, XRD and FTIR measurements. In the presence of Ca(2+) (0.2 mol/L), HAP nanorods showed ultra-high DNA loading capacity, which was significantly enhanced by one or two magnitude compared with the recently reported high loading capacity mesoporous silica vectors. HAP nanorods, therefore, have a great potential as the gene vector to deliver DNA into the cells effectively and safely.

Study on the endocytosis and the internalization mechanism of aminosilane-coated Fe3O4 nanoparticles in vitro.

In this study, the endocytosis and the internalization mechanism of aminosilane-coated Fe(3)O(4) nanoparticles into human lung cancer cell line SPC-A1 was studied compared with human lung cell line WI-38 in vitro. The particle endocytosis behavior was studied by using Transmission Electron Microscope (TEM) and Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). It was found that aminosilane-coated Fe(3)O(4) nanoparticles could be greatly taken up by SPC-A1 human cancer cells (202 pg iron/cell) but not by WI-38 human lung cells (13 pg iron/cell). The particles could be retained in SPC-A1 cells over a number of generations in vitro. Different endocytosis was observed by TEM after SPC-A1 cells were treated with different temperature or with/without Cytochalasin B (Inhibitor of phagocytosis) at 37 degrees C. No nanoparticles were taken up by SPC-A1 after the endocytosis inhibited in low temperature. Restoring the endocytosis activity at 37 degrees C, the process of nanoparticles from coated pit to endosomes and lysosomes was observed by TEM. Endocytosis activity was effectively inhibited by the presence of Cytochalasin B at 37 degrees C, while a lot of nanoparticles were uptaken to the cytoplasm of SPC-A1 cells in the control group. Our results suggest that the process of endocytosis of aminosilane-coated Fe(3)O(4) nanoparticles can efficiently takes place in lung cancer cells and nanoparticles can be kept in cancer cells for generations. Phagocytosis may be involved in the internalization process of aminosilane-coated Fe(3)O(4) nanoparticles.

Synthesis of Ag-Fe3O4 heterodimeric nanoparticles.

We report a general synthetic method for construction of size-controlled Ag-Fe3O4 heterodimeric nanoparticles using the Fe3O4 nanoparticles as the seeds. The Ag-Fe3O4 heterodimeric nanoparticle can be controlled by tuning the size of the Fe3O4 seed and reaction conditions for synthesis of the Ag nanoparticles grown on it. The as-synthesized nanoparticles can be readily converted into aqueous-soluble form with newly introduced functional groups on the surface of Ag-Fe3O4 heterodimeric nanoparticles.

Dendrimer modified magnetite nanoparticles for protein immobilization.

A cascading polyamidoamine (PAMAM) dendrimer was synthesized on the surface of magnetite nanoparticles to allow enhanced immobilization of bovine serum albumin (BSA). Characterization of the synthesis revealed exponential doubling of the surface amine from generations one through four starting with an amino silane initiator. Furthermore, transmission electron microscopy (TEM) revealed clear dispersion of the dendrimer-modified magnetite nanoparticles in methanol solution. The dendrimer-modified magnetite nanoparticles were used to carry out magnetic immobilization of BSA. BSA immobilizing efficiency increased with increasing generation from one to five and BSA binding amount of magnetite nanoparticles modified with G5 dendrimer was 7.7 times as much as that of magnetite nanoparticles modified with only aminosilane. There are two major factors that improve the BSA binding capacity of dendrimer-modified magnetite nanoparticles: one is that the increased surface amine can be conjugated to BSA by a chemical bond through glutaraldehyde; the other is that the available area has increased due to the repulsion of surface positive charge.

[Preparation of surface functional magnetic microspheres and their application in nucleic acid separation and enzyme immobilization].

OBJECTIVE: To Prepare surface functional magnetic microspheres for the separation of vascular endothelial growth factor (VEGF) nucleic acid and lactase enzyme immobilization. METHODS: Using suspension polymerization methods to copolymerize MA-styrene containing magnetite nanoparticles and GMA-styrene also containing magnetite nanoparticles, respectively. Both the carboxyl-modified magnetic microspheres and epoxy-modified magnetic microspheres were obtained. In addition, the chloromethyl-modified magnetic microspheres were prepared by seedy microemulsion. The magnetic microspheres bound with b-gamma IgG were determined by radioimmunoassay (RIA), and the separation of VEGF nucleic acid and lactase enzyme immobilization were performed by carboxyl-modified magnetic microspheres. RESULTS: Transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS) and infrared (IR) spectra showed that the products of polymer magnetic microspheres were monodispersed and that the magnetic particles were uniformly distributed in the microsphere with special functional group on the surface of the microsphere. RIA showed that three kinds of magnetic microspheres could be bound with b-gamma IgG and the absorption of b-gamma IgG reached 75 micrograms/mg, especially for the carboxyl-modified magnetic microspheres. The carboxyl-modified magnetic microspheres can be used for the separation of VEGF nucleic acid by coupling with corresponding primer. Moreover, the immobilized enzyme was proportional to the amount of the carboxyl-modified magnetic microspheres. CONCLUSIONS: The surface functional magnetic polymer microspheres can be bound with active bio-substance, and have a wide application prospect in the fields of biology and medicine.

Rheological Behavior of Titanium Dioxide Suspensions.

The rheological properties of titanium dioxide dispersed in water are measured over a wide range of powder concentrations, temperatures, and pH values. The value of intrinsic viscosity of titanium dioxide measured with an Ubbelohde capillary viscometer is 3.55, which is useful for determining the shape and aggregation property of the particles. The yield stress and steady shear viscosity of titanium dioxide with broad and narrow particle size distributions were measured over a wide range of solid volume fractions on a Brabender rheometer. It is observed that the rheological properties of the suspensions are quite different due to the difference in particle size distributions. Quemada, Casson, and Zhou's models were used to fit the experimental data and useful parameters were obtained. Calculated data are also in good agreement with the experimental data. As expected, the shear viscosity and yield stress decrease with increasing temperature. But when the temperature is around 50 degrees C, yield stress increases with increasing temperature while shear viscosity exhibits a complex behavior. The phenomena are very interesting and special. The Peclet number was used to analyze the shear thickening behavior. Models were also used to describe the shear viscosity under different temperatures and the master plots of the reduced variables eta/eta(infinity) vs t(c)gamma; at different temperatures are superimposed, which means the agreement is fair and the models are suitable to describe the rheological properties of titanium dioxide suspensions. pH effects were investigated on a Rheometrics RFS-II rheometer and it was found that pH can change the surface charge of the particles, which also affects the rheological behavior. The pH at which maximum shear viscosity and yield stress occur is in concordance with the isoelectric point. Copyright 2001 Academic Press.