The nano-magnetic ferrofluid was prepared by chemical coprecipitation and its acute toxicology was investigated. The effective diameter (Eff. Diam. ) of the magnetic particles was about 19.9 nm, and the concentration of the ferrofluid was 17. 54 mg/ml. The acute toxic reaction and the main viscera pathological morphology of mice were evaluated after oral, intravenous and intraperitoneal administration of the nano-magnetic ferrofluid of different doses respectively. Half lethal dose (LD50) > 2104. 8 mg/kg,maximum non-effect dose (ED0) = 320. 10mg/kg with oral; LDs,> 438. 50 mg/kg, EDo = 160. 05 mg/kg with intravenous route; and LDso >1578. 6 mg/kg, ED0 = 320. 10 mg/kg with intraperitoneal administration. Degeneration and necrosis of viscera were not found. So the nano-magnetic ferrofluid, of which toxicity is very low, may be used as a drug carrier.
Ferrosoferric Oxide/chemical synthesis ; Ferrosoferric Oxide/*toxicity ; Magnetics ; Nanostructures/*toxicity

OBJECTIVETo investigate the magnetic resonance (MR) signal features of superparamagnetic iron oxide (SPIO) with different particle size and concentration.

METHODSThe superparamagnetic iron oxide with different concentration and particle size was scanned by magnetic resonance; T1, T2 and T2(*) values of each group were recorded to evaluate the features of MR signals.

RESULTSThe T1 value of SPIO with different particle size had negative linear relationship with concentration. In low concentration the T2 and T2(*) values were elevated markedly with the particle size decreased; while in high concentration the T2 and T2(*)values were elevated gently with particle size decreased. lg(T2), particle size and concentration of SPIO had linear relationship.

CONCLUSIONSSPIO affects magnetic resonance signal mainly with effect on T1 and T2. T2 value can be regarded as the major detection index in the magnetic resonance scan of SPIO. There is a linear relationship among particle size, SPIO concentration and lg(T2) value.

Contrast Media ; pharmacology ; Dose-Response Relationship, Drug ; Ferrosoferric Oxide ; chemistry ; pharmacology ; Humans ; Image Enhancement ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; chemistry ; Particle Size

Effects of different procedures of magnetic nanoparticles into the liposome structure on the distribution of magnetic particles in the liposome were investigated. Magnetic liposomes with high-encapsulating rate of cisplatin (CDDP) were obtained. Fe3O4 magnetic nanoparticles which was modified by organic functional group on surface was synthesized by an one-step modified hydrothermal method. The CDDP magnetic liposomes were prepared by a film scattering-ultrasonic technique and the concentrations of CDDP in the liposomes were measured by graphite furnace atomic absorbance spectroscopy. Magnetic liposomes with different microstructure were prepared by the two different procedures, where the magnetic particles were combined with phospholipid before the film preparation to form liposome in procedure I, and drug solution and the magnetic particles were mixed before hydrating the lipids film to form liposome in procedure II. The liposome structure was observed by transmission electron microscope (TEM). The CDDP magnetic liposomes were prepared by the optimized method which was selected by orthogonal test. Encapsulation rate of the magnetic particles distributed in the phospholipid bilayer through the procedure I was 34.90%. While liposome, produced by the procedure II technique, contained magnetic particles in the interior aqueous compartment, which encapsulation rate was 28.34%. Encapsulation rates of both I and II were higher than that of conventional liposome. The release profile of all the three different liposomes in vitro fitted with a first-order equation. Because of distribution of magnetic particles in the phospholipid bilayer, the skeleton of phospholipid bilayer was changed. The releasing tl/2 of magnetic liposomes produced by the procedure I technique is 9 h, which is shorter than that of the other two liposomes. Assemble of magnetic nanoparticles into the structure of liposome was succeeded by the procedure I, which showed superiority than by procedure II whatever in CDDP liposome encapsulation efficiency and content of the magnetic particles and would ensure sustained-release character.
Antineoplastic Agents ; administration & dosage ; chemistry ; Cisplatin ; administration & dosage ; chemistry ; Drug Compounding ; methods ; Ferrosoferric Oxide ; chemistry ; Liposomes ; chemistry ; Magnetite Nanoparticles ; chemistry ; Nanoconjugates ; administration & dosage ; chemistry ; Particle Size

Coprecipitation method was used to prepare triiron tetroxide magnetic nanoparticles enclosed in L-DOPA, and then EDC was used to activate the carboxyl group of L-DOPA after the nanoparticles were synthesized. The carboxyl group of L-DOPA formed amide bond with specific amino on the aptamer by dehydration condensation reaction. The surfaces of magnetic nanoparticles were modified with aptamer and L-DOPA. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nanoparticle size analysis (SEM), magnetic measurement (VSM) and other testing methods were used to detect the magnetic nanoparticles in different stages. The endothelial progeni-tor cells (EPCs) were cocultured with the surface modified magnetic nanoparticles to evaluate cell compatibility and the combination effect of nanoparticles on EPCs in a short period of time. Directional guide of the surface-modified magnetic nanoparticles to endothelial progenitor cells (EPCs) was evaluated under an applied magnetic field and simulated dynamic blood flow condition. The results showed that the prepared magnetic nanoparticles had good magnetic response, good cell compatibility within a certain range of the nanoparticle concentrations. The surface modified nanoparticles could combine with EPCs effectively in a short time, and those nanoparticles combined EPCs can be directionally guided on to a stent surface under the magnetic field in the dynamic flow environment.
Endothelial Progenitor Cells ; cytology ; drug effects ; Ferrosoferric Oxide ; chemistry ; Humans ; Levodopa ; chemistry ; Magnetite Nanoparticles ; chemistry ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction

We prepared Fe3O4 magnetic nanoparticles (MNPs) with the size of 10 nm by chemical coprecipitation. The effects of six aqueous-organic solvents, including tetrahydrofuran, dioxane, acetone, N, N-Dimethylformamide, methylalcohol, and Dimethyl Sulfoxide, on peroxidase mimetic activity of Fe3O4 MNPs were studied and compared with that of horseradish peroxidase (HRP). The relative activity of Fe3O4 MNPs droped sharply as the elevation of organic solvent concentration increased from 30% to 75% (V/V). In 15% organic solutions, the optimum activity of Fe3O4 MNPs was observed around 50 degrees C, under pH 3.6. After being treated at different temperatures and pH in 15% organic solutions, even under 75% concentration, Fe3O4 MNPs still preserved most of the activity when reacting in aqueous phase. The catalytic performances of Fe3O4 MNPs under given conditions were generally more superior to that of HRP. For it costs lower and it is easy to be prepared and segregated magnetically for recycle, to use the magnetic nanoparticles as a substitution for HRP has potential to be applied into organic catalysis.
Acetone ; chemistry ; Biomimetics ; Catalysis ; Dioxanes ; chemistry ; Ferrosoferric Oxide ; chemistry ; Furans ; chemistry ; Hydrogen-Ion Concentration ; Magnetite Nanoparticles ; chemistry ; Organic Chemicals ; chemistry ; Peroxidase ; metabolism ; Solvents ; Temperature

OBJECTIVETo explore the feasibility of in vivo tracking of bone marrow mesenchymal stem cells (BMSCs) labeled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) in rats after cerebral ischemia, and to analyze the influence of stem cell therapy on the volume of cerebral infarction.

METHODSThe samples of rat bone marrow were collected. BMSCs separated by density gradient centrifugation were cultivated and harvested until the third passage. BMSCs were labeled with SPIO, which was mixed with poly-L-lysine. The labeling efficiency was evaluated by Prussian blue staining. Transient middle cerebral arterial occlusion (MCAO) was performed successfully in 18 adult Sprague-Dawley rats that scored from 6 to 12 by the modified neurological severity test. The 18 rats were then randomly divided into group A, B, and C, with 6 rats in each group and Group C was regarded as control group. BMSCs were injected into the contralateral cortex of ischemia in group A, ipsilateral corpora striata in group B, while D-Hank's solution was injected into ipsilateral corpora striata (group C) 24 hours after MCAO. MRI was performed 1 day after MCAO, 1 day and 14 days after transplantation. The volume of infarcted brain tissue was measured and analyzed. Prussian blue staining of brain tissues was performed to identify the migration of BMSCs.

RESULTSThe labeling efficiency of BMSCs with SPIO was 96%. The transplanted BMSCs migrated to the ischemic hemisphere along the corpus callosum and to the border of the infarction, which was confirmed by MRI and Prussian blue staining. The changes of infarction volume were not significantly different among these three groups.

CONCLUSIONSMRI is feasible for in vivo tracking of BMSCs labeled with SPIO in rats. The stem cell therapy may not be able to affect the volume of cerebral infarction.

Animals ; Brain ; pathology ; Cells, Cultured ; Dextrans ; Disease Models, Animal ; Feasibility Studies ; Ferrosoferric Oxide ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; Male ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling ; methods ; Stroke ; pathology ; surgery

OBJECTIVETo investigate the magnetic resonance (MR) signal changes of superparamagnetic iron oxide (SPIO) and its biological effects on endothelial cells.

METHODSThe citric-acid coated SPIO was synthesized by co-precipitation method. The human umbilical vein endothelial cells (HUVECs) were incubated with SPIO for 24 h in culture medium at iron concentration of 0.01, 0.05, 0.10, 0.15 mg/ml (experimental groups), and the cells incubated without SPIO served as control groups. The uptake efficiency of intracellular iron was measured by Prussian blue staining, and the cell viability was monitored by Calcein-AM method. The cell cytoskeleton (F-actin and tubulin), adherence and migration capacity were measured by immunofluorescence staining. The iron oxide nanoparticles distribution and the cellular organelle change were monitored by transmission electron microscopy (TEM). Quantification of particle uptake was measured by atomic absorption spectrometry. The MR signal of endothelial cells after labeling was monitored by Philips 3.0 T MR scanner.

RESULTSSPIO was uptaken by HUVECs in a concentration-dependence manner. Compared with the control group, cell viability was decreased along with the increase of iron concentration. Compared with the control group, the cell cytoskeleton was markedly disorganized and the FAK spot was bigger and sparser.The nanoparticles were mainly existed in lysosomes, and the higher concentration of SPIO, the more lysosomes and vacuoles presented in the cells. The iron content per cell was (55.86 +/-9.935) pg when the SPIO concentration was 0.15 mg/ml. The MR image showed that the cells labeled with SPIO resulted in the decrease of MR signal.

CONCLUSIONThe cells labeled with SPIO can be detected by MR. The cell viability, cytoskeleton, adherence and migration capacity of HUVECs are affected by citric-acid coated SPIO in a concentration-dependent manner.

Cells, Cultured ; Contrast Media ; pharmacology ; Endothelial Cells ; cytology ; physiology ; Ferrosoferric Oxide ; chemistry ; pharmacology ; Humans ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; chemistry ; Spectrophotometry, Atomic ; Umbilical Veins ; cytology

OBJECTIVETo label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury (TBI) by susceptibility weighted imaging (SWI) sequence.

METHODSBMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley (SD) rats weighing 200-250 g were randomly divided into 4 groups: Groups A-D (n equal to 6 for each group). Moderate TBI models of all the rats were developed in the left hemisphere following Feeney's method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day, one week and three weeks after implantation.

RESULTSNumerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope (200). Scattered little iron particles were observed in the vesicles by electron microscopy (5000). MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images, phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.

CONCLUSIONSWI sequence in vivo can consecutively and noninvasively trace and demonstrate the status and distribution of BMSCs labeled with SPIO in the brain of TBI model rats.

Animals ; Bone Marrow Cells ; cytology ; Brain Injuries ; pathology ; surgery ; Cells, Cultured ; Dextrans ; Ferrosoferric Oxide ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; Male ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley

In this study, polyelectrolyte microcapsules have been fabricated by biocompatible ferrosoferric oxide nanoparticles (Fe3O4 NPs) and poly allyamine hydrochloride (PAH) using layer by layer assembly technique. The Fe3O4 NPs were prepared by chemical co-precipitation, and characterized by transmission electron microscopy (TEM) and infrared spectrum (IR). Quartz cell also was used as a substrate for building multilayer films to evaluate the capability of forming planar film. The result showed that Fe3O4 NPs were selectively deposited on the surface of quartz cell. Microcapsules containing Fe3O4 NPs were fabricated by Fe3O4 NPs and PAH alternately self-assembly on calcium carbonate microparticles firstly, then 0.2 molL(-1) EDTA was used to remove the calcium carbonate. Scanning electron microscopy (SEM), Zetasizer and vibrating sample magnetometer (VSM) were used to characterize the microcapsule's morphology, size and magnetic properties. The result revealed that Fe3O4 NPs and PAH were successfully deposited on the surface of CaCO3 microparticles, the microcapsule manifested superparamagnetism, size and saturation magnetization were 4.9 +/- 1.2 microm and 8.94 emu x g(-1), respectively. As a model drug, Rhodamin B isothiocyanate labeled bovine serum albumin (RBITC-BSA) was encapsulated in microcapsule depended on pH sensitive of the microcapsule film. When pH 5.0, drug add in was 2 mg, the encapsulation efficiency was (86.08 +/- 3.36) % and the drug loading was 8.01 +/- 0.30 mg x m(L-1).
Calcium Carbonate ; chemistry ; Capsules ; Chemical Precipitation ; Drug Carriers ; Drug Compounding ; methods ; Drug Delivery Systems ; Electrolytes ; chemistry ; Ferrosoferric Oxide ; chemistry ; Magnetite Nanoparticles ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Particle Size ; Rhodamines ; administration & dosage ; chemistry ; Serum Albumin, Bovine ; administration & dosage ; chemistry

Adult ; Aged ; Contrast Media ; Dextrans ; Female ; Ferrosoferric Oxide ; Focal Nodular Hyperplasia ; diagnosis ; pathology ; Humans ; Image Enhancement ; Iron ; Liver Cirrhosis ; diagnosis ; pathology ; Liver Neoplasms ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; Male ; Middle Aged ; Oxides