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目的 制备出一种新型的含TNF并具有强烈磁性反应的聚碳酸酯磁性微球 ,并进一步研究其体内对肝细胞癌的靶向治疗作用。方法 采用化学沉淀法制备Fe3 O4 超微磁粉 ,以聚 5 ,5 二甲基 三亚甲基碳酸酯 共 三亚甲基碳酸酯为膜材 ,在低温反应体系下 ,以人血清白蛋白为保护剂 ,采用改进的W /O/W复合溶剂挥发法制备含肿瘤坏死因子的聚碳酸酯磁性微球。研究了此微球制剂体外对肝癌细胞的细胞毒作用 ,并在外加磁场的作用下对人裸鼠肝癌模型进行了靶向治疗实验。结论 该磁性微球具有良好的磁响应性能 ,体外 40 0 0GS磁场下动作距离为 2 6cm/min ,体外对肝癌细胞Bel 740 2有较强的细胞毒作用 ,裸鼠人肝癌模型靶向治疗实验显示 ,在肿瘤部位 5 0 0 0GS条件下 ,静脉用药 3次即有明显抑制肿瘤生长作用 ,其 4周瘤重抑制率为 5 5 .46 % ,明显高于游离药物组 (2 6 .88% ,P <0 .0 0 1)和无磁药物微球组 (2 7.85 % ,P <0 .0 0 1)。结果 本实验为肝癌的生物靶向治疗提供了一种可能的新剂型 ,有较好的临床应用前景
Objective To prepare a novel polycarbonate magnetic microsphere containing TNF and having a strong magnetic response, and further study its targeted therapeutic effect on hepatocellular carcinoma in vivo. Methods Fe3 O4 ultrafine magnetic powders were prepared by chemical precipitation method. Poly-5,5-dimethyl-trimethylene carbonate co-trimethylene carbonate was used as membrane material. In the low-temperature reaction system, human serum albumin was used as protective agent. Polycarbonate magnetic microspheres containing tumor necrosis factor were prepared by modified W/O/W composite solvent evaporation method. The cytotoxicity of this microsphere preparation on hepatocellular carcinoma cells in vitro was studied, and targeted therapy experiments on human hepatoma models of nude mice were performed under the external magnetic field. Conclusion The magnetic microspheres have good magnetic response performance. The action distance is 40 cm in vitro and the operating distance is 2 6 cm/min. It has a strong cytotoxic effect on hepatoma cells Bel 740 2 in vitro. The targeted therapy of human liver cancer model in nude mice According to the results, tumor growth was significantly inhibited by intravenous administration at the tumor site of 500 GS for 3 times, and the tumor weight inhibition rate was 54.46% at 4 weeks, which was significantly higher than that of the free drug group (26.88%). , P <0. 0 0 1) and non-magnetic drug microspheres (2 7.85 %, P <0. 0 0 1). Results This experiment provides a possible new dosage form for biological targeted therapy of liver cancer, and has a good clinical application prospects.