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Objective To track the migration and incorporation of intravenously injected, magneti?cally labeled endothelial progenitor cells ( EPCs) from mouse bone marrow into the blood vessels in a rapid?ly growing HCC model by microMR (7.0 T). Methods This study was approved by the Institutional Com?mittee on Animal Research. H22 hepatic ascitic cancer cells was directly injected into the left liver lobe of BALB/c nude mice ( n=15) . EPCs derived from bone marrow of C57BL/6 mice were isolated and cultured. The third passage EPCs were collected and labeled with 25 μg/ml superparamagnetic iron oxide ( SPIO) and poly?l?lysine (PLL) complex (SPIO?PLL). MTT assay and flow cytometry were used to evaluate the difference of growth curve and apoptosis between labeled and unlabeled EPCs. EPCs labeled with SPIO?PLL were injected into mice via tail vein in experiment group (on the 3rd day after establishing HCC model) (n=15) and control group (n=6). The signal changes of tumor (the 1st, 3rd and 7th day after transplantation) were observed by microMR. Prussian blue staining and immunohistochemistry staining of CD31 were per?formed. MRI findings were confirmed by histomorphology. Two?sample t test was used to analyze the data. Results Single tumor was showed in the liver of all mice 3 d after establishing models. Labeling with SPIO?PLL at a concentration of 25μg/ml did not alter cell growth curve ( measured by MTT assay;t=0.281, P>0.05) and cell apoptosis (analyzed by flow cytometry). The apoptosis rates of SPIO?PLL labeled and un?labled EPCs were (12.31±1.43)% and (11.57±1.24)% in early stage, and (0.55±0.07)% and (0.49± 0?05)% in late stage. No significant differences were observed between them (t=0.967, 1.060; both P>0?05) . Migration and incorporation of transplanted and labeled cells into tumor were documented with in vivo microMR as low signal intensity at the tumor periphery as early as the 3rd day after EPCs administration in preformed tumors (4/5). Prussian blue staining showed iron?positive cells at the sites corresponding to low signal intensity on MRI. The positive cells expressing CD31 existed in intratumoral and peritumoral vessels. There was no signal change in control group at all time points. Conclusions MRI can demonstrate the in?corporation of magnetic labeled mouse EPCs into the implanted hepatoma. It may be helpful for early diagno?sis and therapy of liver tumor.
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Objective To determine the optimal procedure for preparation of the SPIO nanoparticles modified by dextran polylysine,and to evaluate the quality of this product.Methods The optimal preparation procedure of four factors (solution pH value,dextran concentration,reaction temperature and stirring rate) affecting SPIO hydrodynamic size were obtained through orthogonal experiments (3 levels).SPIO nanoparticles were synthesized under an optimum procedure.The shape and hydrodynamic size were detected by transmission electron microscope (TEM) and Malvern Zetasizer respectively.The content of Fe was detected by atomic absorption spectrophotometer,while chemical structures of SPIO nanoparticles were characterized and analyzed by infrared spectroscopy (IR) method.X-ray powder diffraction method was used to identify the ingredients,and the magnetic parameters were measured by vibrating sample magnetometer.Furthermore,experiments with ovarian cancer cells were performed to primarily validate the magnetic property of SPIO nanoparticles.Results The results of the orthogonal experiments showed that the optimum preparation procedure was as follows:dextran concentration of 10 mg/ml,pH 10,reaction temperature of 80 ℃ and stirring rate of 600 r/min.The TEM results showed the SPIO nanoparticles were in spherical shape,homogeneously distributed and uniform in size,and the mean diameter was 7.0 nm.The content of Fe was (12.36±0.08) g/L.The IR results clearly showed that the Fe3O4 was coated by dextran successfully.The Xray powder diffraction method showed that the sample contained Fe3O4 and the magnetism parameters indicated that the sample had superparamagnetism.The experiments with ovarian cancer cells demonstrated that SPIO nanoparticles could enter into the cells and then the cells had certain magnetic properties.Conclusions The SPIO nanoparticles synthesized under the optimal procedure are stable,small in size,with good dispersion and are feasible to enter into cells for rendering certain magnetic properties.This study has provided a good foundation and potential for further research.
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Objective To manufacture magnetic microbubbles with dual-response to ultrasound and magnetic fields.Methods Microbubbles of ultrasound contrast agent (ST68) based on a surfactant were prepared by the acoustic cavitation method.Fe3O4 magnetic nanoparticles with negative charge were synthesized using the polyol procedure.Magnetic microbubbles were generated by depositing polyethylenimine and Fe3O4 magnetic nanoparticles alternately onto the microbubbles using the layer-by-layer self-assembly.In vitro ultrasonography was performed on a silicone tube with/without magnetic microbubbles (3 × 108/ml) by a self-made device to observe the movement of magnetic microbubbles under the effects of magnetic field.In vivo imaging was performed on the kidney of New Zealand rabbits before and after the injection of magnetic microbubbles.Results The Fe3O4 nanoparticles carried a stable negative charge of (-24.6 ± 6.7) mV and more than 98％ of the particles were less than 8 μm in diameter,meeting the size requirement of an ultrasound contrast agent for intravenous administration.There was no echoic signal in the silicone tube before injection of magnetic microbubbles,but there were strong echoic signals after injection.After applying a magnetic field,the magnetic microbubbles moved along the direction of the magnetic flux.In vivo ultrasound imaging could not visualize the kidney before injection of magnetic microbubbles,but could remarkably visualize the kidney after injection.Conclusions The magnetic microbubbles exhibit favorable magnetic targeting and ultrasound contrast enhancement characteristics.Such properties may serve as the foundation to study their potential for simultaneous diagnosis and treatment in the future.
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Objective To study the feasibility of the Fe3O4-loaded lipid perfluorooctylbromide nanoparticles (Fe3O4-PFOB) for enhanced ultrasound imaging.Methods The Fe3O4-PFOB nanoparticles,incubated with RAW264.7 macrophage cells,were monitored by microscope and ultrasound.Twelve SD rats were randomized into two groups,Fe3O4-PFOB group and PFOB group.Ultrasound imaging of rats' liver was performed before and after intravenous injection of the contrast agents.The liver echogenic intensity was quantified by DFY ultrasound quantified system analysis.Results Incubation of the Fe3O4-PFOB nanoparticles with macrophages resulted in the uptake of Fe3O4-PFOB by macrophages.Macrophages loaded with Fe3O4-PFOB exhibited enhanced echogenicity in vitro.In in vivo imaging,Fe3O4-PFOB produced better and prolonged ultrasound enhancement of rats' liver compared to PFOB nanoparticles.Conclusions Fe3O4-PFOB nanoparticles could enhance ultrasound imaging and may potentially serve as a multimodal probe for ultrasound,CT and MR imaging.
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Objective To track the magnetically labeled bone marrow mononuclear stem cells (BM-MNCs) in canine myocardial infarction (MI) model with MR. Methods BM-MNCs were labeled with Feridex effectively in vitro and then injected intramyocardially in 8 MI model dogs. Serial MR was performed with 1.5T MR scanner to show the location of the labeled cells compared with histology. Results The injection sites of labeled BM-MNCs could be located on the 1st and 2nd week, but disappeared on the 4th week. Corresponding to these sites, Prussian blue staining consistently showed that large clusters of cells were labeled by dense intracellular iron at the scar tissue. Conclusion Feridex labeling BM-MNCs enables ready detection in the beating heart on a conventional MR scanner after transplantation into canine infarcted myocardium.
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Objective To explore the optimal situation of labeling bone mesenchymal stem cells (BMSCs) with superparamagnetic iron oxides (SPIO) mediated by poly-L-lysine (PLL), and determine the most optimal protocol of magnetic resonance imaging according to the patterns of MR in vitro. Methods BMSCs were isolated from white rat and purified, incubated with SPIO-PLL complexes at the range of concentrations (0, 4.2, 8.4, 21, 42, 84 ?g Fe per ml medium). The labeling ratio and distribution of SPIO particles in BMSCs, and the morphological evidence of abnormal visualization were evaluated by Prussian blue staining, fluorescent microscope and electron microscopy. MTT growth curves and magnetic resonance imagings were obtained at the range of concentrations. Trypan blue exclusion test was performed to elevate the viability of BMSCs labeled with PLL at the range of concentrations (0, 0.05, 0.25, 0.5, 1.0, 5.0 ?g PLL per ml medium). Results The cellular labeling ratio was strongly correlated to the concentrations of SPIO (P
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0.05).When the concentration of ferumoxides exceeded 22.4?g/ml,there was significant difference(P