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OBJECTIVE: To synthesize immunomagnetic nanoparticles with uniform particle size, strong superamagnetism as well as strong immune activity which can be specifically and sensitively combined with circulating tumor cells in peripheral blood of patients with breast cancer.METHODS: Superparamagnetic oxide iron nanoparticles containing active carboxyl groups (SMNP-COOH) were synthesized by polyol methods, thermogravimetric analysis was used to determine the amount of carboxyl groups on the surface of SMNP-COOH, while the content of iron was determined by o-phenanthroline. Mediated by 1-ethyl-3,3-dimethylaminopropyl carbodiimide(EDC) and N-hydroxysuccinimide (NHS), immunomagnetic nanoparticles(IMNP) against human breast carcinoma cell line were constructed by binding the monoclonal antibodies against hMAM with SMNP-COOH. X-Ray diffraction was used to confirm their synthesis,meanwhile,transmission electron microscope (TEM), dynamic light scattering (DLS), and vibrating sample magnetometry (VSM) were applied to characterize their physicochemical properties. The conjugation amount of the antibodies and the activity of IMNPs were evaluated by enzyme linked immunosorbent assay (ELISA).RESULTS: X-Ray diffraction showed that the chracteristic peaks of the crystalline powder of SMNP-COOH and IMNP agreed with the Fe3O4 standard. The concentration of iron in SMMP-COOH and IMNP were 0.205 and 0.164 mol•L-1, respectively.TEM showed that both synthesized SMNP-COOH and IMNP were almost spherical or ellipsoidal. The sizes of SMNP-COOH and IMNP were (13.7±3.6) and (15.4±4.5) nm, respectively. Dynamic light scattering(DLS) demonstrated the intensity particle size and polydispersity index (PDI) of SMNP-COOH and IMNP were 23.4 nm and 0.303, and 71.2 nm and 0.175,respectively. VSM results showed that both SMNP-COOH and IMNP had strong superamagnetism, and the saturation magnetization of SMNP-COOH and IMNP were 71.37 and 67.68 emu•g-1Fe, respectively, which confirmed antibody binding may reduce the magnetism of SMNP-COOH. The ELISA results showed the conjugation amount of antibody was about 93 μg on 1 mg SMNP-COOH by covalent bond. The obtained immunomagnetic nanoparticles (IMNP) which were bound with the hMAM monoclonal antibodies could specifically and sensitively combine with breast cancer cell line MDA-MB-415.CONCLUSION: IMNP with strong superparamagnetic property,excellent stability and perfect antibody activity were successfully synthesized, which demonstrate the potential to magnetically separate circulating tumor cells in peripheral blood from patients with breast cancer, thus providing a favorable weapon to accurately detect CTCs in breast tumor patients.
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OBJECTIVE: To explore how to carry out pharmaceutical consultation for anti-infection treatment in neutropenic hematological patients with invasive fugal disease and elaborate the value of clinical pharmacists in anti-infection treatment. METHODS: A total of 41 hematologic malignancies patients with invasive fungal disease who were consulted by clinical pharmacist from October 2014 to June 2016 were enrolled into the study. The etiology, bacteria complication, and infection site were summarized. The other 41 agranulocytosis patients complicated with invasive fungal disease without clinical pharmacist consultation randomly sampled by HIS were used as the control. Statistical analysis were carried out to evaluate the effect of anti-infection treatment. The authors also discussed that as a clinical pharmacist how to carry out pharmaceutical consultation through several typical anti-fungal infection cases. RESULTS: Totally 45 strains of fungi were isolated from the secretion specimens obtained from the 41 patients, including Candida albicans, Candida glabrata, Candidakrusei, Candida tropicalis, Aspergillums, and Cryptococcosis, among which Candida albicans accounted for 60.0%, followed by Aspetgillus (13.3%), Candidakrusei (11.1%), Candida glabrata (6.67%), Candida tropicalisi (6.67%), and Cryptococcosis (2.2%). The main infection site was the lung, followed by the digestive tract and blood stream. The positive rate of bacteria culture was 58.5% among the 41 patients, and the major isolated bacteria were Escherichia colis, Pseudomonas aeruginosa, Enterococcus, and Pseudomonas maltophilia. For the antifungal treatment involving the clinical pharmacists, the cure rate was 48.8%, the significant effective rate was 34.2%, the improved effective rate was 7.4%, the total effective rate of treatment was 72.9%, and the failure rate was 9.3%. There was significant difference in the curative effect between the clinical pharmacist consultation group and the control group (P<0.05). CONCLUSION: The incidence of fungal infection in agranulocytosis patients is high, and most of the patients are complicated with bacteria infection. The most frequently infected site is respiratory tract. Clinical pharmacists can play an important role in the treatment of invasive fungal disease in agranulocytosis patients to ensure the treatment safety and efficacy.
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OBJECTIVE: To improve superparamagnetic iron oxide nanoparticles (SPIO-NP) stability, biocompatibility and tumor-targeting and evaluate their tumor targeting in vitro. METHODS: The folic acid-carboxymethylchitosan-superparamagnetic iron oxide nanoparticles (FA-OCMCS-SPIO-NPs) were synthesized by "three-steps": at first, superparamagnetic oxide iron nanoparticles were synthesized by coprecipitation, then, O-carboxymethyl chitosan and folic acid were successfully immobilized on the surface of SPIO-NPs in turn. The fourier transform infrared spectroscopy, X-Ray diffraction were used to confirm their synthesis, meanwhile, transmission electron microscope (TEM), dynamic light scattering (DLS), Zeta-potential measurement and vibrating sample magnetometry (VSM) were applied to characterize their physicochemical properies. Ferrozine assay and Prussian blue staining were used to evaluate their tumor targeting in vitro. RESULTS: X-Ray diffraction showed the crystalline powder of FA-CMCS-SPIO-NPs agree with the standard Fe3O4, Fourier transform infrared results showed O-carboxymethylchitosan and folic acid were covalently modified on the surface of SPIO-NPs successfully, TEM showed all synthesized SPIO-NPs were almost spherical or ellipsoidal. Their sizes were less then 20 nm, dynamic light scattering (DLS), Zeta-potential results demonstrate the intensity particle size distributions of FA-OCMCS-SPIO-NPs were (41.4±0.132)nm, Zeta potential were (-21.36±15)mV. The surface modification may lead to decrese of magnetisms Ferrozine assay and Prussian blue staining results showed FA-OCMCS-SPIO-NPs had good tumor targeting and the tumor targeting had good relations with the amount of FR on surface of tumor cells. CONCLUSION: FA-OCMCS-SPIO-NPs with strong superparamagnetic property, excellent stability, and good folate receptor targeting is successfully synthesized, which demonstrated the potential for tumor MRI diagnose and therapy.
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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.