| Purpose:Select a magnetic media for the comprehensive cancer treatment, aims to enhance the therapeutic effect, reduce the toxic side effects of single treatment, and improve the patient’s quality of life and extends survival. Choose the micron-scale ferromagnetic media for cancer treatment through in vitro and in vivo temperature experimental. The subject in vitro evaluation of the microemulsion as the thermo-chemotherapy embolism media of biocompatibility and further explore the feasibility of its as a liver rumor embolism thermo-chemotherapy media for liver tumor. The microemulsion was fabricated by applying iodized oil as the matrix, in which anti-tumor drug doxorubicin (DOX),and magnetic nanoparticles(MNPs). Micro-iron oxide used for the situ embolization medium’s initial select.Methods:Micron ferromagnetic media selection:First, purchasing from International Specialty Products (ISP) company carbonyl iron powder (CIP) carried out morphological characteri-zation, followed by temperature properties were measured in vivo and in vitro. Finally the sample of Fe3O4purchasing from different manufacturers and different size samples were characterized, biocompatibility properties and temperature measurement. The sample of Fe3O4Were cleaned by following order:distilled water, dried over anhydrous ethanol, dichloromethane, ethanol, distilled water. After dry installs in small bottle. Using scanning electron microscopy(SEM), laser particle size analyzer, vibrating sample magnetoeter (VSM) meter analysed each sample. Preparation of sample extracts which was according to Evalution on Biology of Medical Apparatus GB/T16886.521997(cell toxicity test method in vitro), incubation with L-929cell, cell viability and cell toxicity grade was evaluated by CCK-8assay. Determination heating performance for Fe3O4sample after cleaning Heating performance measurement for carbonyl iron inside and outside.Oleic acid-modified MNPs The preparation, characterization and determination of temperature conditions of modified with oleic acid(OA-MNPs):The MNPs was synthetised by chemical coprecipitation method, the method of MNPs surface modified with oleic acid by mechanical agitation. The product was analyzed by transmission electron microscopy (TEM), thermal gravimetric analysis(TGA), Fourier transform infrared spectrometer (FTIR), vibrating sa-mple magnetometer(VSM). An inductive heating property was evaluated by monitoring the temperature increase of the nanocomposite microemulsion under an alternative magnetic field (AMF).Drug-loaded magnetic nanocomposite iodized oil microemulsion’s biocompatibility and heat chemotherapy and anti-tumor efficacy of verification in vitro:Drug-loaded magnetic nanocomposite iodized oil microemulsion was prepared by using the double emulsion method. The microemulsion was fabricated by applying iodized oil as the matrix, in which anti-tumor drug doxorubicin(DOX),and magnetic nanoparticles(MNPs), emulsifier polyoxyethylene hydrogenated castor oil40(HCO40). Mouse fibroblast cell L-929and human liver hepatocellular carcinoma cell HepG-2were for the employed in the study, cell viability was evaluated by CCK-8assay. L-929was purpose to evaluate cell toxicity grade. HepG-2was subjected to various treatments including AMF exposure30min, drug treatment,heating treatment as well as thermochemotherapy treatment medicated by the nanocomposite microemulsion.Results:SEM images show that the carbonyl iron powder particle morphology rules into a ball; The sample of Fe3O4particle’s morphology was irregular, particle size was heterogeneity. The results of heating temperature in vitro under500kHz alternating magnetic field show that each sample have a good temperature performance. Biocompatibility results show that the cytotoxicity level of each sample is0or1, having a good biocompatibility, can be used for subsequent experiments. The result of Carbonyl iron heating in tumor and the sample of2#,7#,9#,11#in vitro tissue wanning results show that heating effect is ineffective, can not meet the needs of hyperthermia temperature.OA-MNPs for TEM images:The average size of oleic acid modified magnetic nanoparticle was uniform, taking a spherical shape, surface with a layer of film, having aggregation. FTIR result show that at the wavelength of the2922cm-1,2850cm-1,1406cm-1appeared four special absorption peaks. TGA analysis, weightlessness at350～800℃show oleic acid molecules has linked to MNPs. oleic acid modified magnetic nanoparticles were Super paramagnetic, and their Saturation magnetization was slightly lower than magnetic nanoparticles. The medium has a heating good performance under the alternating magnetic field; meet the demand of the hyperthermia temperature.Cytotoxicity study reveals the microemulsion showed good biocompatibility,which meets the requirement to Evolution on Biology of Medical Apparatus. Magnetic induction hyperthermia combined with DOX chemotherapy greater efforts to inhibit the proliferation of liver cancer cells, the presence of two proven co-sensitizing effect.Conclusion:Micron Fe3O4and carbonyl iron biocompatibility meet Biological evaluation of medical national standard requirements of the medium, but at a performance owed. Micron-level medium for comprehensive cancer treatment to be further screened. This study proposes drug-loaded nanomagnetic iodized oil microemulsion is a new functional media for liver tumors’ comprehensive treatment. It not only own good biocompatibility,but also have good heating performance in the alternating magnetic field and achieve the clinical needs, meanwhile achieving heat chemotherapy synergistic sensitizing effects. |
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