| Tumor tissues are very sensitive to high temperature than normal cells, therefore, with a low resistance to temperature. Based on this, an increasement of local temperature is introduced to kill cancer cells, which is called thermotherapy (hyperthermia), is becoming a very important way of cancer therapy. Magnetic fluid hyperthermia (MFH), cause little damage to human body, with well targeting property, can be used in tumor therapy alone, or combined with other treatment methods to achieve synergies, thus becoming a research emphasis in the tumor hyperthermia.Iodized oil is an embolism agent in the treatment of liver cancer, and it needs to be used in conjunction with other cancer treatment methods to enhance therapeutic effect. Fe3O4/iodized oil magnetic fluid, is prepared with iodized oil and Fe3O4 nanoparticles (MNPs) which has magnetocaloric property, could selectively deposit in liver for a long time under the action of iodized oil, to achieve arterial embolization and hyperthermia, will have very important practical value in cancer treatment, especially for liver cancer.Fe3O4 is known as a kind of magnetic material with low toxicity, good stability and excellent magnetic properties, which is commonly used in the preparation of magnetic fluids. In order to get effective hyperthermia in tumor therapy, Fe3O4 needs to have good biocompatibility and high specific absorption rate. For hydrophilic 4, surface modification is needed to form a uniform and stable dispersion of in iodized oil, but the modification process usually complicate, easy to introduce impurities and reduce the magnetic property. For hydrophobic Fe3O4, the common used preparation methods need high temperature, which will affect the application of Fe3O4. In this article, oleylamine is used as solvents, reducing agents and surface modification agent, hydrophobic MNPs with high saturation magnetization were synthesized by solvothermal method in a relatively low temperature. The effects of different reactants, solvents and additives were studied using XRD, SEM, VSM and other testing methods. And then, MNPs were dispersed in iodized oil to prepare MNPs/iodized oil magnetic fluid, which is used in tumor hyperthermia. The main contents of this article are:(1) Organic iron Fe(acac)3 as the research object to prepare hydrophobic MNPs, different solvents, reaction time and additives were studied. The results showed that 5mL phenyl ether and 20mL oleylamine reacted at 200℃ for 9h, the products were hydrophobic MNPs, and the saturation magnetization was 48emu/g. 10mL oleylamine and 10mL ethylene glycol (EG) as reaction agents, reacted at 200℃ for 8h, can get hydrophobic MNPs with high purity, good crystallization properties, and the saturation magnetization was 76.8emu/g. Stearic acid and oleic acid as additives, could improved the crystallization properties of MNPs, but reduce the magnetic properties because of the additive coating.(2) The synthesis of MNPs using inorganic iron salts, EG and oleylamine as reagents was studied. Research results showed that FeCl3·6H2O2 as precursor,200℃ for 8h could get MNPs, the products with good hydrophobicity, well crystallized, spherical like, and high saturation magnetization, which was 90emu/g. This preparation method had the advantages of relatively low temperature, low cost, simple, and no secondary pollution which is caused by modification. The MNPs morphology, particles size and magnetic properties were affected by the ratio of EG and oleylamine, Fe3+ concentration, and the additives. The higher of oleylamine content, the smaller of particles size. Increasing the content of EG, MNPs with hollow structures can be obtained.The particles size also can be changed by differernt Fe3+ concentration. The structures of MNPs were turened to clusters with the addition of oleic acid. And stearic acid could restrain the particle growth, with the amount of lmmol, MNPs’ average diameter reduced from 71.38nm to 41.73nm.(3) The synthesis and growth mechanism of MNPs were studied. oleylamine was the main reducing agent, phenyl ether or EG were important supplements. The growth mechanisms of Fe3O4 particles can be divided into Oswald ripening, gas as soft templates and self-assembly of particles.(4) MNPs specimens were dispersed in iodized oil to form MNPs/iodized oil magnetic fluids (MF), the stability was evaluated. MF stability mainly influence by the particles morphology and size. MNPs prepared with 3mmolFeCl3-6H2O, 10mL oleylamine, 10mL EG and 0.8mmol stearic acid could be suspended in iodized oil stably for more than 30 days. Heat effections of magnetic fluids in alternating magnetic field were researched, the highest SAR value of magnetic fluids could reach 117.8W/g. The affects of MNPs content and current on MF magnetocaloric effect were studied. Energy dissipation P is proportional to the magnetic field strength and frequency. If the particles size is greater than 17nm, P is inversely proportional to the particles size. Both the specific saturation magnetizations and the average diameters of MNPs were important factors which affect the SAR values of the magnetic fluids.(5) Direct contact method was used to evaluate the cytotoxicity of MNPs, MNPs concentration as the main influence factors. MNPs/iodized oil MF injected into the mice tumor, showed good magnetocaloric effects, the temperature could reach the thermotherapy temperature of more than 42℃, causing a significant apoptosis of tumor cells.The heat therapy had no effect on surrounding tissues,which was local hyperthermia. Pathology results confirmed tumor cells around MF were killed after hyperthermia, iodinated oil embolism could also cause the death of tumor cells. Heart and lung showed no significant lesions when MF was used for a long time. But MF could deposit in the liver, which means MF may be targeted to the liver. |
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