This study was purposed to investigate the effects of magnetic nanoparticle of Fe3O4 (Fe3O4-MNPs) on murine immune system. ICR mice were assigned randomly into four groups which were treated with normal saline, low, middle and high dose of MNP-Fe3O4 respectively. The mice were killed after being exposed by intragastric administration for 2 weeks. The ratios of spleen weight to body weight, lymphocyte transformation rate in spleen suspension and phagocytic index of macrophage in abdominal cavity were detected. The results showed that the ratios of spleen weight to body weight in Fe3O4-MNP groups were not significantly different in comparison with the control (p > 0.05). The lymphocyte transformation rate in spleen suspension in Fe3O4-MNP groups were all higher than that in control group (-0.1775 +/- 0.0246), especially in the middle dose group (0.1833 +/- 0.0593) (p < 0.05), and the phagocytic index of macrophages in abdominal cavity of middle dose group (0.2051 +/- 0.0213) was higher than that of control group and other two Fe3O4-MNP group (low dose 0.1538 +/- 0.0100, high dose 0.1511 +/- 0.0184) (p < 0.05). It is concluded that suitable dose of Fe3O4-MNP can enhance the cellular immune activity and phagocytic function of macrophages of mice.
Animals ; Immunity, Cellular ; Lymphocytes ; drug effects ; Macrophages ; drug effects ; Magnetite Nanoparticles ; administration & dosage ; Mice ; Mice, Inbred ICR ; Phagocytosis

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

OBJECTIVETo study magnetic resonance enhancement features of inflammatory lymph nodes using different doses of ultrasmall superparamagnetic iron oxide (USPIO) particles in order to establish a standardized protocol for USPIO enhanced magnetic resonance imaging of lymph nodes.

METHODSA total of 12 healthy New Zealand rabbits were injected complete Freund's adjuvant in foot pad to establish popliteal inflammatory lymph node model. Different doses (45, 90, 135 micromol Fe/kg) of USPIO were injected intravenously. Magnetic resonance scans were performed before and after USPIO injection to observe the enhancement features of different groups. T2 signal intensity, T1 signal intensity, T2 x value, and T2 value were measured and T2 enhancement ratio was calculated at different time points.

RESULTSTwenty-four hours after USPIO injection, there was no statistical difference in T2 signal intensity and T2 enhancement ratio between 90 and 135 micromol Fe/kg dose groups, but both were superior to 45 micromol Fe/kg group (P < 0.05). There were no statistical differences in T2 signal intensity, T1 signal intensity, T2 value, and T2 enhance ratio among different postcontrast time delays from 6 to 24 hours in 90 micromol Fe/kg group (P > 0.05), and signal reduction of lymph nodes peaked 18 hours after USPIO injection. Better images were acquired with a postcontrast delay of 18-24 hours.

CONCLUSIONSLymph nodes can be enhanced well with a dose of 90 micromol Fe/kg. Postcontrast delay of 18-24 hours is appropriate for acquiring satisfactory enhancement images.

Animals ; Contrast Media ; administration & dosage ; Dextrans ; administration & dosage ; Image Enhancement ; methods ; Lymphadenitis ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; administration & dosage ; Male ; Rabbits ; Random Allocation

OBJECTIVETo investigate the feasibility of in vivo magnetic resonance imaging (MRI) tracking of transplanted adipose-derived stem cells (ADSCs) labeled with superparamagnetic iron oxide (SPIO) in rat heart.

METHODSADSCs were labeled with poly-L-lysine (PLL)-SPIO complexes. Intracellular iron uptake was identified by Prussian blue stain and transmission electromicroscopy. Trypan blue staining was used to test the viability of the labeled cells. In vitro MRI of labeled cells was performed. SPIO-labeled ADSCs were transplanted into normal rat hearts and were in vivo imaged with MRI. Image findings on MRI were correlated with histological findings of the rat hearts.

RESULTSThe labeling efficacy of ADSCs with PLL-SPIO was nearly 100%. Light microscopy revealed the SPIO particles were located in the cytoplasm of the ADSCs by Prussian blue staining. Transmission electromicroscopy revealed that the SPIO particles were located in the endosomes in the cytoplasm. There was no significantly deference in viability between labeled and unlabeled groups demonstrated by Trypan blue test (P > 0.05). MRI showed signal loss in gel mixed with labeled cells as compared with the unlabeled cells group and blank group. Signal void on rat hearts were demonstrated on MRI and were well correlated with histological findings where Prussian-blue-stain positive cells presented.

CONCLUSIONMRI can be used to in vivo track the transplanted ADSCs labeled with SPIO into rat hearts and facilitate to understand the conditions of the labeled cells in the transplanted areas.

Adipocytes ; cytology ; Animals ; Cell Differentiation ; Contrast Media ; administration & dosage ; Dextrans ; administration & dosage ; Feasibility Studies ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; administration & dosage ; Male ; Myocardium ; cytology ; pathology ; Rats ; Rats, Wistar ; Stem Cell Transplantation ; methods ; Stem Cells ; cytology

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.
Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Survival ; drug effects ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; Ferrosoferric Oxide ; chemistry ; Humans ; Hyperthermia, Induced ; MCF-7 Cells ; Magnetite Nanoparticles ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry

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

OBJECTIVETo investigate the effect of target therapy with cisplatin (CDDP)-loaded magnetic nanoparticles (MNP) in combination with chemoradiotherapy against nasopharyngeal carcinoma cell growth in nude mice.

METHODSThirty-six BALB/c mice with implanted tumor of CNE-2 cells were randomly divided into 6 groups (n=6), including the control group, radiotherapy group, CDDP group, CDDP plus radiotherapy group, CDDP-MNP group, and CDDP-MNP plus radiotherapy group. The mice were given 0.3 ml normal saline (control) or corresponding agents (3 mg/kg) via the tail vein, and 0.5 ml saline was administered intragastrically before the injections. Before and after the treatment, the body weight, tumor volume and weight, and the tumor inhibition rates were measured. The proliferating cell nuclear antigen (PCNA) index was calculated on the basis of immunohistochemical staining.

RESULTSExcept for the cisplatin group, all the treated groups showed significantly reduced tumor volume as compared with that in the control group (P<0.05) with lowered body weight. Compared with the cisplatin group, the combined treatment groups showed significantly higher tumor inhibition rate (P<0.05), but the effect showed no significant difference from that in the radiotherapy group (P>0.05).

CONCLUSIONTargeted therapy with CDDP-loaded MNP alone or in combination with radiotherapy can effectively inhibit the growth of nasopharyngeal carcinoma in nude mice without increasing the toxicity.

Animals ; Carcinoma ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Drug Delivery Systems ; Female ; Magnetite Nanoparticles ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Neoplasm Transplantation

OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. MATERIALS AND METHODS: The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin(R))-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.
3T3 Cells ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/chemistry/*drug therapy ; Cell Line, Tumor ; Drug Delivery Systems/methods ; Female ; Ferric Compounds/chemistry ; Humans ; Liposomes ; Magnetite Nanoparticles/administration & dosage/*chemistry ; Mice ; Molecular Targeted Therapy/methods ; Nanoconjugates/administration & dosage/*chemistry ; Nanoparticles/chemistry ; *Receptor, erbB-2/immunology ; Silicon Dioxide/administration & dosage/*chemical synthesis/chemistry

Folic acid-O-carboxymethyl chitosan ultrasmall superparamagnetic iron oxide nanoparticles (FA-OCMCS-USPIO-NPs) are a novel molecular targeting MR contrast agent. This paper reperts the pharmacokinetics and magnetic resonance response characteristics of FA-OCMCS-USPIO-NPs in normal rats and mice, and discussed its distributing regularity in animals, providing basis for tumor targeting imaging. O-phenanthroline method was used to determine iron content in rats' plasma and mice's organs following high and low doses of nanoparticles injected through tail vein, and the blood concentration-time curve was drawn, the calculated t1/2 of two groups were greater than 7 h. The results of tissue distribution showed that only a small part of nanoparticles were swallowed by the liver and spleen, while none in the heart, lung and kidney. At the same times, the phagocytosis of nanoparticles did not change with the dose. The results of MRI showed that renal excretion occurred 4 hours after injection, and signal to noise ratio (SNR) of liver and kidney returned to normal levels 24 hours after injection. There were no nanoparticles in the lungs. So a part of nanoparticles escaped from phagocytosis of liver and spleen, and it owned lower toxicity and longer half-life. indicated its use for tumor-targeting imaging. All of these indicated its use for tumor-targeting imaging.
Animals ; Area Under Curve ; Chitosan ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Contrast Media ; administration & dosage ; chemistry ; pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Carriers ; Ferric Compounds ; administration & dosage ; chemistry ; pharmacokinetics ; Folic Acid ; administration & dosage ; chemistry ; pharmacokinetics ; Injections, Intravenous ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; administration & dosage ; chemistry ; Male ; Mice ; Nanoparticles ; Particle Size ; Phagocytosis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

AIMTo investigate whether the biological process of superparamagnetic iron oxide (SPIO)-labeled human mesenchymal stem cells (hMSCs) may be monitored non-invasively by using in vivo magnetic resonance (MR) imaging with conventional 1.5-T system examinations in corpus cavernosa of rats and rabbits.

METHODSThe labeling efficiency and viability of SPIO-labeled hMSCs were examined with Prussian blue and Tripan blue, respectively. After SPIO-labeled hMSCs were transplanted to the corpus cavernosa of rats and rabbits, serial T2-weighted MR images were taken and histological examinations were carried out over a 4-week period.

RESULTShMSCs loaded with SPIO compared to unlabeled cells had a similar viability. For SPIO-labeled hMSCs more than 1 X 10 (5) concentration in vitro, MR images showed a decrease in signal intensity. MR signal intensity at the areas of SPIO-labeled hMSCs in the rat and rabbit corpus cavernosa decreased and was confined locally. After injection of SPIO-labeled hMSCs into the corpus cavernosum, MR imaging demonstrated that hMSCs could be seen for at least 12 weeks after injection. The presence of iron was confirmed with Prussian blue staining in histological sections.

CONCLUSIONSPIO-labeled hMSCs in corpus cavernosa of rats and rabbits can be evaluated non-invasively by molecular MR imaging. Our findings suggest that MR imaging has the ability to test the long-term therapeutic potential of hMSCs in animals in the setting of erectile dysfunction.

Animals ; Cell Survival ; Contrast Media ; administration & dosage ; Dextrans ; Ferrosoferric Oxide ; Humans ; Iron ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Oxides ; Penis ; pathology ; Rabbits ; Rats ; Staining and Labeling ; methods