This study was purposed to evaluate whether the safe concentration of magnetic nanoparticles of Fe₃O₄(MNPs-Fe₃O₄) for monocytes could induce the SKM-1 cell apoptosis. The average size and Zeta potential of MNPs-Fe₃O₄were determined by transmission electron microscopy and the Malvern Zetasizer 3000 HS, respectively. The cell viability after being exposed to MNPs-Fe₃O₄for 12, 24, 48, and 72 hours was detected by using cell count Kit-8. The cell apoptosis was evaluated by flow cytometry with Annexin V/PI double staining and Wright-Giemsa staining. The cell cycle was measured by flow cytometry. The levels of active caspase-3, survivin and bcl-rambo in cells treated with MNPs-Fe₃O₄and/or trolox for 48 hours were detected with Western blot. The results showed that the cell viability decreased in SKM-1 cells after exposure to 50 µmol/L and 100 µmol/L MNPs-Fe₃O₄(P < 0.05), but did not in monocytes (P > 0.05), compared with that of each non-MNPs-Fe₃O₄-treated group. This exposure also induced the SKM-1 cells to be arrested in G0/G1. Annexin V/PI staining assay showed that cell apoptotic rate induced by 100 µmol/L MNPs-Fe₃O₄was significantly high in SKM-1 cells while not so high in monocytes, and the pretreatment with trolox could attenuate the apoptosis. Moreover, the active caspase-3 increased in SKM-1 cells after the exposure to MNPs-Fe₃O₄, while that was not in monocytes, and the increased expression of BCL-rambo and the decreased expression of survivin involved in the process were also observed. It is concluded that MNPs-Fe₃O₄can induce the caspase 3-dependent SKM-1 cell apoptosis by increasing the BCL-rambo expression and decreasing the survivin expression, but this cytotoxic effect can not be observed in monocyte's.
Apoptosis ; drug effects ; Caspase 3 ; Cell Cycle ; Cell Line, Tumor ; Ferric Compounds ; pharmacology ; Flow Cytometry ; Humans ; Magnetics ; Metal Nanoparticles ; administration & dosage

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

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

OBJECTIVE: To investigate the effect of different intravenous iron treatment regimens on anemia and oxidative stress in maintenance hemodialysis (MHD) patients. METHODS: A total of 58 MHD patients were randomly divided into a multi-frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8 weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose 100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20). Another 20 healthy people served as a control group (n=20). The changes of hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and after the treatment. RESULTS: After 8 weeks, compared with the non-iron group, the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly elevated (P<0.01), but there was no difference between the two iron groups (P>0.05). After the single dialysis, the two iron groups had higher level of serum MDA, MPO and lower level of serum SOD than that of the non-iron supplementation group (P<0.01). The multi-frequency low-dose intravenous iron group had lower level of serum MDA [(5.37 ± 0.73) nmol/mL vs (6.37±1.67) nmol/mL], MPO [(81.41±7.60) U/L vs (96.75±16.97) U/L] and higher level of serum SOD [(84.77 ± 14.02) U/mL vs (68.23 ± 4.90) U/mL] than that of the less-frequency regular-dose intravenous iron group. After 8 weeks, there was no significant difference between the two iron groups (P>0.05). CONCLUSION Multi-frequency low-dose intravenous iron can effectively improve anemia in MHD patients, whose acute oxidative stress is lower than that of less-frequency regular-dose intravenous iron, and is a relatively safe and effective intravenous iron treatment regimen.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia ; drug therapy ; etiology ; Female ; Ferric Compounds ; administration & dosage ; Ferric Oxide, Saccharated ; Glucaric Acid ; Humans ; Injections, Intravenous ; Kidney Failure, Chronic ; complications ; drug therapy ; Male ; Middle Aged ; Oxidative Stress ; drug effects ; Renal Dialysis ; Sucrose ; administration & dosage ; Young Adult

Iron deficiency anemia (IDA) frequently occurs in infants and adolescents. IDA is the result of an interplay between increased host requirements, limited external supply, and increased blood loss. In outpatient clinics, we often see children with iron deficiency anemia. Most cases in children are caused by incomplete nutrient supplements and growth spurts. However, we can occasionally see patients with poor response despite iron supplementation. Failure of iron therapy occurs when a child does not receive the prescribed medication, when iron is given in a form that is poorly absorbed, or when there is a continuing unrecognized blood loss such as intestinal or pulmonary loss, or loss with menstrual periods. In addition, the therapeutic failure of iron medication may indicate that the original diagnosis of nutritional iron deficiency was incorrect. In this situation, we have to evaluate other etiologies of anemia. Recently, many cases relating H.pylori infection to iron deficiency anemia have been described in the literature and H.pylori infection has emerged as a cause of refractory iron deficiency anemia that is unresponsive to oral iron therapy. Also, iron deficiency anemia induced by athletics in adolescent females has been reported several times. In this article, the author reviews various etiologies of childhood iron deficiency anemia. The most important consideration in treatment of iron deficiency anemia is disclosure of the underlying cause and its recovery. Dietary habits should also be corrected. To supplement iron, 6 mg/kg of oral iron supplements (elemental iron) is recommended in ferrous salt form. If oral administration is not feasible, intravenous supplementation is recommended using forms such as iron dextran, iron gluconate, or iron sucrose.
Administration, Oral ; Adolescent ; Ambulatory Care Facilities ; Anemia ; Anemia, Iron-Deficiency ; Child ; Dextrans ; Disclosure ; Female ; Ferric Compounds ; Food Habits ; Glucaric Acid ; Gluconates ; Humans ; Infant ; Iron ; Sports ; Sucrose

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

Recently, nanometer-sized magnetic particles have been intensively concerned and investigated due to their particularly large surface-to-volume ratio, quantum-size effect, magnetic character as well as their potential application in the area of bioscience and medicine. The most promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification, which have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, drug delivery, hyperthermia and cell separation. To focus on one of the most important and fascinating subjects in nanobiotechnology, this review describes the current situation and development of magnetic iron oxide nanoparticles and their applications in drug delivery and hyperthermia in tumor-targeted therapy. The possible perspectives and some challenges to further development of these nanoparticles are also analyzed and discussed.
Animals ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Delivery Systems ; methods ; Ferric Compounds ; administration & dosage ; chemistry ; therapeutic use ; Humans ; Hyperthermia, Induced ; methods ; Magnetics ; Nanoconjugates ; administration & dosage ; chemistry ; therapeutic use ; Neoplasms ; drug therapy ; therapy ; Particle Size

Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B12, vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.
Aged ; Aged, 80 and over ; Anemia/*drug therapy ; Arthroplasty, Replacement, Hip/*adverse effects ; Blood Transfusion ; Drug Therapy, Combination ; Erythropoietin/*administration & dosage ; Female ; Ferric Compounds/*administration & dosage ; Humans

This study was aimed to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (Fe(3)O(4)-MNPs) combined with DNR in vivo. The xenograft leukemia model with stable multiple drug resistance in nude mice was established. The two sub-clones of K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1 x 10(7) cells/each) to establish the leukemia xenograft models. Drug resistant and the sensitive tumor-bearing nude mice were both assigned randomly into 5 groups: group A was treated with NS; group B was treated with DNR; group C was treated with nanoparticle of Fe(3)O(4) combined with DNR; group D was treated with 5-BrTet combined with DNR; group E was treated with 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were carried out. The protein levels of BCL-2, BAX, and Caspase-3 in resistant tumors were detected by Western blot. The results indicated that 5-BrTet and magnetic nanoparticle of Fe(3)O(4) combined with DNR significantly suppressed growth of K562/A02 cell xenograft tumor, histopathologic examination of tumors showed the tumors necrosis obviously. Application of 5-BrTet and magnetic nanoparticle of Fe(3)O(4) inhibited the expression of BCL-2 protein and up-regulated the expression of BAX, and Caspase-3 protein in K562/A02 cell xenograft tumor. It is concluded that 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR have significant tumor-suppressing effect on MDR leukemia cell xenograft model.
Animals ; Antineoplastic Agents ; pharmacology ; Benzylisoquinolines ; pharmacology ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Female ; Ferric Compounds ; administration & dosage ; Humans ; K562 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nanoparticles ; administration & dosage ; Xenograft Model Antitumor Assays

The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe(3)O(4) and 5-Bromotetrandrine (5-BrTet) on chronic leukemia. The apoptosis was detected by flow cytometry (FCM), Wright staining and light microscope; the expressions of BAX and BCL-2 were measured by Western blot. The results showed that combination of daunorubicin (DNR) with either MNP (Fe(3)O(4)) or 5-BrTet exerted a potent cytotoxic effect on K562/A02 cells, while MNP (Fe(3)O(4)) and 5-BrTet co-treatment could synergistically enhance DNR-induced apoptosis. After treated with this regimen, the typical apoptotic morphological features were found in K562/A02 cells; the expression level of BCL-2 decreased and BAX increased markedly. It is concluded that MNP (Fe(3)O(4)) or 5-BrTet with DNR can induce apoptosis in K562/A02 cells, and they show distinct synergism when used together. The down-regulation of BCL-2 and the up-regulation of BAX may play important roles.
Apoptosis ; drug effects ; Benzylisoquinolines ; pharmacology ; Daunorubicin ; pharmacology ; Down-Regulation ; Ferric Compounds ; administration & dosage ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Nanoparticles ; administration & dosage ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Up-Regulation ; bcl-2-Associated X Protein ; metabolism