【作者】 王杰；

【导师】 何丹农； 朱君；

【作者基本信息】 上海交通大学 ， 材料工程（专业学位）， 2018， 硕士

【摘要】 肺部是人体内非常重要的部位,随着环境的日益恶劣,肺部疾病的危害日益变大。肺部肿瘤和缺氧造成的急性肺损伤是其中两种非常严重的肺部疾病,针对这两种疾病,本论文基于氟碳化合物的优良特性开展了治疗研究。针对以上两种肺部疾病,本论文以全氟化碳为研究对象,选取PLGA作为PFOB的载体,研究表明全氟化碳具有非常多优异的性能,尤其是强大的溶氧能力,输氧能力可达到40%,同时拥有更好的体内安全性。因此本课题开发出两种肺部亲和型氟碳化合物纳米粒对肺部进行保护与治疗。1.制备PLGA-PEG/PFOB乳剂。通过细胞实验来表征复合乳剂对于细胞的影响,确定乳剂有良好的体内安全性,并且一定程度上可促进A549细胞的生长,低氧浓度下对细胞活性有一定的提升效果,对低氧处理复氧后细胞活性也有一定的回复作用。ROS和HIF-1α表达水平的测定验证了细胞恢复与凋亡之间的平衡机制。之后通过建立动物的肺灌洗模型和缺氧环境模型证明乳剂对于肺部通气的改善有明显的作用,肺组织切片和肺顺应性性进一步说明乳剂可作为表面活性剂,在雾化进入到肺部后即时性地降低表面张力,改善肺部的顺应性以及肺部通透性。2.本课题建立了一种负载光敏剂和氟碳化合物的纳米微囊PFOB-PLGA-IR780,解决肿瘤内部的低氧抑制治疗问题,达到增益PDT和改善热疗的效果,进而增加肿瘤治疗效果。体外和体内的光热曲线都表明具有良好的光热转换性能。同时对细胞和体内肿瘤的PDT和PTT联合治疗试验都证明纳米微囊对肿瘤细胞和肺部肿瘤的生长有非常显著的抑制作用,PFOB的加入提高了PDT的治疗效果,显著增强了治疗效果。通过上述实验,可证明全氟化碳材料可以作为治疗肺部肿瘤和急性肺损伤的一个重要研究对象,未来在肺部疾病方面有非常好应用前景。更多还原

【Abstract】 Lung is a tremendously significant part of human body.Acute lung injury caused by hypoxia and lung tumor are two very serious lung diseases.For these two diseases,we have carried out research based on the excellent characteristics of fluorocarbons.In view of the above two kinds of lung diseases,we choose PFCs as the research object and PLGA as PFOB carrier.Some researches show that perfluorocarbon(PFCs)has many excellent properties,especially the strong ability of dissolving oxygen(40%).Therefore we have developed two kinds of fluorocarbon nanoparticles for the protection and treatment of the lungs.1.PLGA-PEG/PFOB emulsion was prepared successfully.The cell experiments were used to characterize the effect of composite emulsion on cells.The emulsion was proved that has good biocompatibility and can promote the growth of A549 cells to a certain extent under low oxygen concentration.It also plays a significanted role in recovery from hypoxia reoxygenation experiments.The evaluation of the expression level of ROS and HIF-1 alpha confirmed the balance mechanism between cell recovery and apoptosis.Then the saline lavage acute lung injury model and hypoxia environment model have been builded to proved that the emulsion have obvious effect on improving pulmonary ventilation.Lung histological sections and lung compliance further show that it can be used as a surfactant to reduce surface tension and improve lung compliance and permeability.2.we have established PFOB-PLGA-IR780 nanocapsule loaded with photosensitizers and fluorocarbons,which can improve oxygen concentration of tumors.And the effect of PDT also can be improved because of PFOB.The photothermal curves in vitro and in vivo show that the photothermal conversion performance is very good.At the same time,the growth of A549 cells and lung tumors both have been inhibited by the combination therapy.The addition of PFOB increased the therapeutic effect of PDT and significantly enhanced the therapeutic effect.Through these experiments,we can prove that PFC materials can be used as an important research object in the treatment of lung cancer and acute lung injury.更多还原