OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5x105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microgram/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL.
Cells, Cultured ; Contrast Media/chemical synthesis/pharmacokinetics ; Cross-Linking Reagents/chemistry ; Ferric Compounds/chemistry/*pharmacokinetics ; Ferrosoferric Oxide/chemical synthesis/pharmacokinetics ; Gene Products, tat/chemistry ; Humans ; Iron/*pharmacokinetics ; Magnetic Resonance Imaging/methods ; Nanoparticles ; Neural Tube ; Oxides/*pharmacokinetics ; Phantoms, Imaging ; Polylysine/pharmacokinetics ; Spectrophotometry, Atomic ; Staining and Labeling/*methods ; Stem Cells/cytology/*drug effects/metabolism ; Time Factors ; Transfection

OBJECTIVETo prepare matrine double-sensitive colon-specific pellets and study the factors affecting its quality and evaluateing the colon-specific effects of preparation.

METHODMatrine enzyme-sensitive pellets core were prepared by carboxymethyl konjac glucomannan as the main carrier material, and coated the core by acrylic resin II and III to prepare matrine double-sensitive colon-specific pellets. The prescription and technology of the matrine colon-specific pellets were studied by the single factor investigation, through the in vitro release test and coating rate determination.

RESULTThe optimized process conditions: FeCl3 concentration is 4.0 g x L(-1), chitosan concentration is 3.0 g x L(-1), carboxymethyl konjac glucomannan concentration is 20 g x L(-1), mixed gel solution pH value is 3. The release of matrine is less than 30% in the simulation of the upper gastrointestinal medium. The release of matrine is close to 100% in simulated full gastrointestinal medium, the coating weight is 7%.

CONCLUSIONThe prepared pellets have good colon positioning effect in vitro.

Acrylic Resins ; chemistry ; Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Chitosan ; chemistry ; Chlorides ; chemistry ; Colon ; metabolism ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Ferric Compounds ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Mannans ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Reproducibility of Results ; Tablets, Enteric-Coated ; Time Factors

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

OBJECTIVETo compare the differences in uptake of 2-deoxy-D-glucose (2-DG)-conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high metabolism and breast fibroblasts with normal metabolism, and investigate the feasibility of using the coated nanoparticles as a MRI-targeted contrast agent for highly metabolic carcinoma cells.

METHODSThe γ-Fe2O3@DMSA-DG was prepared. The glucose metabolism level of both cell lines was determined. The targeting efficacy of γ-Fe2O3@DMSA-DG and γ-Fe2O3@DMSA NPs to breast carcinoma MDA-MB-231 cells and breast fibroblasts at 10 min, 30 min, 1 h and 2 h was measured with Prussian blue staining and UV colorimetric assay. MRI was performed to visualize the changes of T2WI signal intensity.

RESULTSPrussian blue staining showed more intracellular blue granules in the MDA-MB-231 cells of γ-Fe2O3@DMSA-DG NPs group than that in the γ-Fe2O3@DMSA NPs group, and the γ-Fe2O3@DMSA-DG uptake was greatly competed by free D-glucose. As revealed by UV colorimetric assay, MDA-MB-231 cells also showed that the cellular iron amount of γ-Fe2O3@DMSA-DG group was significantly higher than that of the γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG + D-glucose group, statistically with a significant difference between them. MRI showed that the signal intensity of γ-Fe2O3@DMSA-DG group was decrease significantly, the T2 signal intensity was decreased by 10.5%, 37.5%, 72.9%, 92.0% for 10 min, 30 min, 1 h and 2 h, respectively. In contrast, the signal intensity did not show obvious decrease in the γ-Fe2O3@DMSA-DG group, the T2 signal intensity was decreased by 8.5%, 11.4%, 32.0%, 76.7% for 10 min, 30 min, 1 h and 2 h, respectively. However, HUM-CELL-0056 cells did not produce apparent difference for positive staining in the γ-Fe2O3@DMSA-DG group, γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG+D-glucose group, and the signal intensity also did not produce apparent difference.

CONCLUSIONSγ-Fe2O3@DMSA-DG has good targeting ability to highly metabolic breast carcinoma (MDA-MB-231) cells. It is feasible to serve as a specific MRI-targeted contrast agent for highly metabolic carcinoma cells, and deserves further studies in vivo.

Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Colorimetry ; methods ; Contrast Media ; pharmacokinetics ; Deoxyglucose ; chemistry ; pharmacokinetics ; Female ; Ferric Compounds ; chemistry ; pharmacokinetics ; Fibroblasts ; cytology ; metabolism ; Glucose ; metabolism ; Humans ; Iron ; metabolism ; Magnetic Resonance Imaging ; methods ; Nanoconjugates ; chemistry ; Particle Size ; Succimer ; chemistry ; pharmacokinetics

OBJECTIVETo evaluate the role of 2-deoxy-D-glucose (2-DG) modified supermagnetic iron oxide nanoparticles (SPIO) (γ-Fe2O3@DMSA-DG NPs) in tumor detection as a magnetic resonance imaging (MRI) contrast agent.

METHODSγ-Fe2O3@DMSA-DG NPs was prepared. The degree of A549 cells targeted absorption of γ-Fe2O3@DMSA-DG NPs was detected by Prussian blue staining, colorimetric assay, T2W and multi-echo sequence MRI. γ-Fe2O3@DMSA NPs was used as a control agent, and free D-glucose as a competitive inhibitor. Human lung adenocarcinoma A549 xenograft tumor was prepared in nude mice. Sterile aqueous suspension of γ-Fe2O3@DMSA NPs or γ-Fe2O3@DMSA-DG NPs was injected into the tail vein of nude mice. Before and 6, 12, 24, 48 h after injection, MRI imaging of the mice was performed. T2 signal intensity of the tumor, brain, liver and thigh skeletal muscles, and T2 values of the tumors were measured.

RESULTSThe average diameter of the particles was about 10 nm, and there were no significant differences between the diameters of γ-Fe2O3@DMSA NPs and γ- Fe2O3@DMSA-DG NPs. The IR spectra showed the C-N retractable vibration peak at γ-Fe2O3@DMSA-DG NPs surface, indicating that 2-DG was conjugated to the γ-Fe2O3@DMSA NPs. The Prussian blue staining, colorimetric assay, MRI T2 signal intensity and T2 values revealed that γ-Fe2O3@DMSA-DG NPs were significantly more absorbed by A549 cells at growth peak than γ-Fe2O3@DMSA NPs, and the absorption of γ-Fe2O3@DMSA-DG NP was inhibited by free D-glucose. The results of in vivo examination showed that before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA-DG NPs, the mean T2 signal intensities of the tumors were (326.00 ± 16.26)s, (276.40 ± 5.13)s, (268.40 ± 30.58)s, (240.40 ± 25.93)s, (262.20 ± 30.04)s, respectively, and the T2 values of the tumors were (735.80 ± 20.93) ms, (645.80 ± 69.58) ms, (615.00 ± 124.61) ms, (570.60 ± 67.78) ms, and (537.80 ± 105.29) ms, respectively. However, before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA NPs, the mean T2 signal intensities of the tumors were (335.60 ± 4.93)s, (290.80 ± 5.93)s, (273.40 ± 15.08)s, (327.40 ± 16.65)s, and (313.20 ± 20.45)s, respectively, and T2 values were (686.00 ± 21.44)ms, (617.80 ± 69.93)ms, (645.20 ± 85.89)ms, (669.40 ± 13.72)ms, and (608.80 ± 61.90)ms, respectively. The T2 signal intensity and T2 value of the tumors were not declined generally after injection. The liver T2 signal intensity was decreased after injection of both γ-Fe2O3@DMSA-DG NPs and γ-Fe2O3@DMSA NPs, and T2 signal intensity of the brain and muscle did not show significant changes.

CONCLUSIONSγ-Fe2O3@DMSA-DG NPs has an ability to target glucose receptors overexpressed in tumors, and may serve as a MRI contrast agent for tumor detection.

Adenocarcinoma ; diagnosis ; metabolism ; pathology ; Animals ; Cell Line, Tumor ; Colorimetry ; Contrast Media ; chemistry ; pharmacokinetics ; Deoxyglucose ; chemistry ; pharmacokinetics ; Ferric Compounds ; chemistry ; pharmacokinetics ; Humans ; Image Enhancement ; Lung Neoplasms ; diagnosis ; metabolism ; pathology ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Particle Size