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Deoxyglucose-modified Magnetic Nanoparticles Mediated Tumor Magnetic Induction Hyperthermia And Imaging

Posted on:2012-05-05Degree:MasterType:Thesis
Country:ChinaCandidate:Y J ZhengFull Text:PDF
GTID:2204330335458866Subject:Microbial and Biochemical Pharmacy
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Purpose:To investigate the anticancer effect of magnetic induction hyperthermia mediated by 2-deoxy-D-glucose modified magnetic nanoparticles and research the feasibility of thses nanoparticles as a contrast enhancement agent of MRI The tumor-targeting and molecule imaging ability of 2-deoxy-D-glucose modified magnetic nanoparticles was proved in vitro, their anticancer effect and MRI contrast enhancement capacity was investigated in vivo.Methods:The final production---2-deoxy-D-glucose modified magnetic nanoparticles was prepared by using Chemical coprecipitation and Glutaraldehyde crosslinking. The physical and chemical properties of these nanoparticles was charactered by Fourier transform infrared spectroscopy, X-ray diffraction, Vibrating sample magnetometer, thermal analysis, Transmission electron microscopy, and Zeta electric potential test. Effect of alternative magnetic field on the temperature rise of 2-deoxy-D-glucose modified magnetic nanoparticles and MRI imaging ability of these nanoparticles was performed with different concentration. In vitro cytotoxicity study was carried out to test the biocompatibility of 2-deoxy-D-glucose modified magnetic nanoparticles; The tumor-targeting ability was proved by Prussian blue staining, cell sections, Inductively coupled plasma mass spectrometry, and molecule MRI imaging after incubating with different cells at different time points. In vivo study, the subcutaneous tumor model in nude mice was established. After intratumoral injection of 2-deoxy-D-glucose modified magnetic nanoparticles, the mice were prepared for MRI imaging next day and hyperthetmia in 47℃immediately. The therapy effect was evaluated by measuring changes in tumor volume and observing the survival situation.Results:The average size of single 2-deoxy-D-glucose modified magnetic nanoparticle was about 10nm, and Aggregation average size was about 100nm. the amount of amino-silane surface coating was approximately 3%. 2-deoxy-D-glucose modified magnetic nanoparticles were Superparamagnetic, and their Saturation magnetization was 65.19 emu/g. their surface electric charge was 11.1 mV. The heating profile of 2-deoxy-D-glucose modified magnetic nanoparticles was excellent, which can fit the heating requirements of vivo study,and they also has good MRI imaging capability in vitro. In vitro cytotoxicity study showed that the cytotoxicity grade of 2-deoxy-D-glucose modified magnetic nanoparticles was Grade 0, which reveals that these nanoparticles showed no cytotoxicity and has excellent biocompatibility for further investigation. In vitro targeted uptake study demonstrated that cancer cells such as U251 which has high expression of glucose transporter protein can targeted uptake 2-deoxy-D-glucose modified magnetic nanoparticles. In vivo study, compare to the control group, Magnetic induction hyperthermia can inhibit tumor growth and prolong survival effectively, and 2-deoxy-D-glucose modified magnetic nanoparticles showed a sharp contrast enhancement in MRI imaging.Conclusion:The findings demonstrated that 2-deoxy-D-glucose modified magnetic nanoparticles have a significant ability in cancer targeting and MRI imaging. They can also be a brilliant mediator of magnetic induction hyperthermia which induced inhibition of tumor growth.
Keywords/Search Tags:2-deoxy-D-glucose, Magnetic nanoparticles, Magnetic induction hyperthermia, MRI imaging, Targeted
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