| PurposeThis project aims to develop of drug-loaded magnetic nanocomposite implants which have a potential clinical application. The implants load anticancer drug docetaxel and Fe3O4nanoparticles to new biodegradable copolymer matrix. The implants not only have the drug controlled release function but also mediated tumor local magnetic hyperthermia. To complete the magnetic nanocomposite implants biocompatibility evaluation of medical devices on the basis of optimizing the drug-loaded magnetic nanocomposite implants preparation conditions and followed the standards of safety evaluation of the relevant biological materials; human breast cancer cells MCF-7as the object of study to complete the drug-loaded magnetic nanocomposite implants of cell toxicity to clear thermochemotherapy synergistic sensitizing effect; study of subcutaneous tumor model to evaluate anti-tumor effects of the nude mice tumor model, its feasibility as a tumor magnetic induction chemotherapy medium of sustained release hot-depth discussions, to provide experiments and theoretical basis for clinical trial.Methods1. Preparation of drug-loaded magnetic nanocomposite implants and characterization of physical and chemical properties1.1Preparation of drug-loaded magnetic nanocomposite implants and parameter optimization:The Fe3O4nanoparticles were synthesized by chemical co-precipitation method; The Drug-loaded nanocomposite implants were prepared by the solvent cast method using new biodegradable material as the matrix which contained anti-cancer chemotherapy drug docetaxel and Fe3O4magnetic nanoparticles. To optimize their physical properties, TPGS was added.1.2Characterization of physical and chemical properties:The morphology, warming properties in the alternative magnetic field (AMF), tensile properties and in vitro drug release properties were analyzed by modern means to clear the influence of magnetic field conditions, TPGS, the magnetic induction heating up to the drug-loaded magnetic nanocomposite implants and to determine the preparation process parameters of the implants and subsequent biological experimental conditions. 2. Biocompatibility evaluation of magnetic nanocomposite implantsFollowing the National Standards of China T16886.5(GB/medical instrument biology evaluation part5:in vitro cytotoxicity test), mice fibers L929cell line was applied for the in vitro biocompatibility test. Cell morphology and growth state as indicators to comprehensive evaluation of magnetic nanocomposite implants by direct contact method.3. Cytotoxicity of drug-loaded magnetic nanocomposite implants to breast cancerHuman breast cancer cell line MCF-7co-cultured with the drug-loaded magnetic nanocomposite implants to take treatment of thermochemotherapy, docetaxel injection which commonly used in clinical were compared. Cell morphology and relative growth rate (RGR) as indicators to comprehensive evaluation of the in vitro anti-tumor effect of the drug-loaded magnetic nanocomposite implants.4. Anti-tumor profile of drug-loaded magnetic nanocomposite implants studyHuman breast cancer MCF-7cells were applied for this test. The suspension of MCF-7cells was injected subcutaneously into nude mice to imitate human breast cancer model. Nude mice underwent surgical resection of the tumor2/3volume, more than1/3of tumor simulation of breast cancer after resection of the residual tumor bed, the use of intraoperative implantation of the composite implants attached to the postoperative tumor bed. Comprehensive analysis and evaluation of tumor volume in nude mice survival time and pathological examination as an indicator of the composite implants nude mice tumor model of postoperative anti-tumor properties.Results1. The drug-loaded magnetic nanocomposite implants have relatively flat uniform surface; they have flexibility, good tensile properties, can be heated up under alternative magnetic field.2. Magnetic nanocomposite implants have good biocompatibility, no significant cytotoxicity, have little effect on cell morphology and proliferation.3. Drug-loaded magnetic nanocomposite implants in vitro killing effect on human breast cancer cell line MCF-7was significantly better than the clinical injection group and other groups; there is thermochemotherapy synergistic sensitizing effect. 4. Compared to the control group, the drug-loaded magnetic nanocomposite implants kill tumor cells effectively, inhibit tumor growth of nude mice, prevent tumor recurrence, and can extend the survival of nude mice.ConclusionThe drug-loaded magnetic nanocomposite implants can be used as the media to breast cancer magnetic induction thermochemotherapy for their biocompatibility and local thermochemotherapy, and they should be further studied to have clinical applications. |
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