Carry Oxaliplatin, Herceptin Composite Metal Nanoparticles On Molecular Targeting HER2-positive Of Gastric

Background:Gastric cancer is a major illness serious harm to human life and health, the World Health Organization cancer control program data show that new cases of gastric cancer worldwide each year about930,000, about700,000deaths, accounting for all cancer mortality1/10; of each new issue gastric cancer patients up to40million people, the death toll reached300,000, prevalence and mortality are two times more than the world average. Currently in the detection rate of early gastric cancer in China is less than10%. More than90%of patients with gastric cancer in advanced stage when treatment is over, or at the time of diagnosis or disseminated metastasis has occurred, thus losing the opportunity of surgery. Thus, the chemical treatment of gastric cancer is the primary method of treatment of gastric cancer patients most domestic, in our study has important significance. However, the current routine clinical use of systemic chemotherapy drug side effects, poor patient tolerance; tumor cells to chemotherapeutic drug resistance, etc., are easily lead to failure of chemotherapy. Gastric conventional systemic chemotherapy dosage, side effects for large studies, has great value to the academic, social effects and applications. In recent years, due to a variety of nanoparticles can be ideal for a variety of substances in the body and passed with adjustable surface chemistry targeted structure makes it highlights the unique advantage in cancer therapy.Objection:In this study, human gastric cancer cells to epidermal growth factor receptor targeting based on precious metals Au nanoparticles formed by exchange coupling with Fe3O4nanocomposite as a carrier, a monoclonal antibody Herceptin and chemical bonding line chemotherapy Osage Lee platinum, which is constructed to HER2-targeted MRI tracer release oxaliplatin novel nanocomposite oxaliplatin-Au-Fe3O4-Herceptin, and evaluate its value in human epidermal growth factor2-positive gastric cancer.Method1. Even legitimate application switching technology and thermal degradation iron acetylacetonate gold surface degradation to complete construction of Au-USPIO metal nanocomposites. By adding a surface modifier on the morphology of SPIO nanoparticles regulation. TEM characterization of nanoparticles;2. Liquid Oxaliplatin-Au-Fe3O4-Herceptin with a1-a bond formed by mixing ethyl carbodiimide and N-hydroxy succinyl thiosulfate, then mixed with Herceptin was cultured to form-(3-dimethylaminopropyl)-3Au-Fe3O4-Herceptin. Purification by flash chromatography to give the connecting member oxaliplatin. Mixed oxaliplatin suspension, Au-Fe3O4-Herceptin and connecting ligand to optimize the ratio of training to give Oxaliplatin-Au-Fe3O4-Herceptin. MALDI-MS product was verified in vitro binding efficiency of the dialysis bag Taxol at different pH values;3. MTS method were verified Au-Fe3O4, Au-Fe3O4-Herceptin, Oxaliplatin-Au-Fe3O4-Herceptin cytotoxicity;4. Routinely cultured HER2-positive gastric cancer cell lines SGC-7901. Respectively, and Au-Fe3O4, Oxaliplatin-Au-Fe3O4-Herceptin incubated for2hours, TEM degree nanocomposites in gastric cancer cell surface endocytosis;5. Creating and grouped orthotopic xenograft model of gastric cancer:study of gastric cancer in nude mice injected different time model Oxaliplatin-Au-Fe3O4-Herceptin adjust the parameters established MRI scans to observe changes in tumor tissue in mice.Results1. TEM, see nanoparticle size of about25nm, iron particles with gold particles1:1constant;2. Successfully constructed Oxaliplatin-Au-Fe3O4-Herceptin nanocomposite and by mass spectrometry, infrared and dialysis bag oxaliplatin-release button confirms the connection between the molecules are connected by chemical. Cytotoxicity experiments showed that:when the concentration of iron ions within30ug/ml time, Oxaliplatin-Au-Fe3O4-Herceptin nanocomposites basically not toxic to cells;3. in vitro endocytosis experiment:Oxaliplatin-Au-Fe3O4-Herceptin nanocomposites, Fe3O4-Au nanoparticles with the same concentration of iron particles with SGC-7901cells were incubated for2h TEM visible, Oxaliplatin-Au-Fe3O4-Herceptin nanoparticles swallowed by a large number of complex cells, and Fe3O4-Au nanoparticles into cells seen engulfed within;4. mice after intravenous injection of nanoparticle composites for some time, MRI scans mice xenografts, see the tumor tissue relative to low-density signal T2lesions. After staining of tumor tissue Prussia beside a large number of tumor blood vessels iron particles aggregation. ConclusionThis topic through interdisciplinary research, the successful development of metal nano-paclitaxel for HER2receptor compounds Oxaliplatin-Au-Fe3O4-Herceptin, can be combined with paclitaxel targeting anti-cancer, and to achieve MRI tracer release, obtained with independent intellectual property rights. In vivo studies clearly the role and mechanism of action of the compounds of biological safety, and provide a solid experimental and clinical applications for further personalized treatment of patients with HER2-positive gastric cancer, and the development of new drugs. At the same time, also the development of new targeted therapies and targeted therapies provide new ideas and technical support.