超支化聚磷酸酯纳米药物引导的化疗协同光热疗法用于逆转乳腺癌细胞耐药的研究

发布时间：2018-06-03 20:14

本文选题：超支化聚磷酸酯 + 光热疗法　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:研究超支化聚磷酸酯纳米药物引导的光热疗法用于逆转乳腺癌细胞多药耐药。方法:1.构建包载阿霉素和或IR-780的PEG化的超支化聚磷酸酯纳米药物(NP/DOX、NP/IR-780和NP@DOX+780)的输送系统。通过纳米沉淀法以PEG化的超支化聚磷酸酯为基础构建载药颗粒,并对其进行表征,包括粒径、表面电势、在介质中释放行为及光热曲线。2.利用多药耐药肿瘤细胞MCF-7/ADR及MCF-7为模型,使用构建好的包载阿霉素和或IR-780的PEG化的超支化聚磷酸酯纳米药物(NP/DOX、NP/IR-780和NP@DOX+780)的输送系统,研究其逆转乳腺癌多药耐药的行为及效果。利用荧光分光光度计检测纳米颗粒内DOX的浓度。通过流式细胞仪、激光扫描共聚焦显微镜检测细胞摄取,利用MTT实验证明其对细胞的抑制作用。3.以多药耐药肿瘤细胞MCF-7/ADR构建动物模型。通过小动物成像监测纳米药物的脏器分布及肿瘤富集。并通过肿瘤抑制曲线研究纳米药物化疗联合光热治疗的治疗效果,通过小鼠的体重计精神状况观察、药物的毒副反应。结果:1.成功设计和合成含有磷酸酯键和PEG的超支化聚合物,其可以自组装成核-壳纳米颗粒。该设计策略实施以有效克服肿瘤药物抗性并且显示出改善癌症治疗巨大潜力。2.细胞试验中,通过流式细胞仪、激光扫描共聚焦显微镜检测细胞摄取,证明NP/DOX通过内吞方式进入细胞,在细胞内释放出药物,并可避开P-gp的作用,使DOX在MCF-7/ADR细胞中富集。利用MTT实验证明其对细胞的抑制作用,与游离DOX相比,NP/DOX可显著增加对细胞的杀伤作用,有效克服肿瘤细胞耐药性。3.动物实验证明了光热疗法和化疗疗法的联合应用具有更高的疗效并且可逆转耐药细胞肿瘤模型中的耐药性。结论:成功地合成了PEG化的超支化聚磷酸酯,联合化疗和光热疗法用于逆转癌症中的耐药性,其通过EPR效应具有较长的循环时间和在肿瘤组织内的富集作用,并且提供了克服耐药性的巨大潜在癌症治疗策略。
[Abstract]:Objective: To study the use of hyperbranched polyphosphate nanoscale guided photothermal therapy to reverse multidrug resistance of breast cancer cells. Methods: 1. the delivery system of PEG based hyperbranched polyphosphate nanodrugs (NP/DOX, NP/IR-780 and NP@DOX+780) containing adriamycin and or IR-780 was constructed. Through the nano precipitation method, the hyperbranched polyphosphoric acid polyphosphate was used as PEG. The basic construction of drug carrying particles and characterization, including particle size, surface potential, release behavior in the medium and photothermal curve.2. using multidrug resistant tumor cells MCF-7/ADR and MCF-7 as models, use the construction of a PEG encapsulated hyperbranched polyphosphate nanoscale (NP/DOX, NP/IR-780 and NP@DOX+780) containing adriamycin and or IR-780 PEG. The system was used to study the behavior and effect of multidrug resistance in breast cancer. The concentration of DOX in nanoparticles was detected by a fluorescence spectrophotometer. Cell uptake was detected by flow cytometry, laser scanning confocal microscope, and MTT experiment proved that.3. was used to construct animal model of multidrug resistant tumor cell MCF-7/ADR. Monitoring the viscera distribution and tumor enrichment of nanoscale drugs by small animal imaging, and study the therapeutic effect of nano drug chemotherapy combined with photothermal therapy through the tumor inhibition curve, through the observation of the mental state of the body weight meter of mice and the toxic and side effects of the drug. Results: 1. the hyperbranched polymer containing phosphate key and PEG was successfully designed and synthesized. It can be self assembled into nuclear shell nanoparticles. The design strategy is implemented to effectively overcome tumor drug resistance and to demonstrate the potential for improving cancer treatment potential.2. cell tests, using a flow cytometer, laser scanning confocal microscopy to detect cell uptake, proving that NP/DOX passes endocytosis into the cell and releases the drug in the cell. It can avoid the effect of P-gp and enrich the DOX in MCF-7/ADR cells. Using MTT experiment, the inhibition effect on cells is proved. Compared with free DOX, NP/DOX can significantly increase the killing effect on cells, and effectively overcome the drug resistance of tumor cells.3. animal experiments proved that the combination of photothermotherapy and chemotherapy therapy has a higher effect. And it can reverse the drug resistance in the drug-resistant cell tumor model. Conclusion: the PEG hyperbranched polyphosphate is successfully synthesized. Combined chemotherapy and photothermal therapy can be used to reverse the drug resistance in cancer. The EPR effect has a long cycle time and enrichment in the tumor tissue, and provides a huge potential for overcoming resistance. Cancer treatment strategy.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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