二氢卟吩新药对胆管癌的荧光定位成像与光动力治疗作用研究

Cholangiocarcinoma is a malignant tumor of with high fatality rate. As the incidence in a unique position, a significant impact on the life, the low rate of early diagnosis, poor prognosis, the mortality rate is almost as high as the incidence rate. Only less than 40% of Cholangiocarcinoma patients are able to carry out surgery, but easily relapse after surgery. In addition, the efficacy of radiation therapy and chemotherapy on cholangiocarcinoma is not ideal. Therefore, new method for the treatment of cholangiocarcinoma is urgent to be developed. Photodynamic diagnosis and photodynamic therapy are new methods for the diagnosis and treatment of cancer in recent years, which have good prospects with advantages of efficient, minimally invasive, and higher selective. The objects of our study include two new chlorin drugs, Temoporfin and Talaporfin, which are listed abroad, as well as kinds of novel chlorin photosensitizers which are prepared by our team. This project studies the characteristics of fluorescence imaging of the new drug in the cholangiocarcinoma, and the anti-cancer mechanism of above photosensitizers by researching the photosensitizer on cells, tissues, animal, molecular and immunological levels. The structure-activity relationships of novel chlorin compounds and the key technical parameters of cholangiocarcinoma PDT will be summarized. These will be of great value to develop new candidate drugs to cholangiocarcinoma with the independent intellectual property rights, with targeted, efficient, cheap characterics and with no skin phototoxicity, and to promote the popularization and application of photodynamic therapy in clinics.

胆管癌是一种致死率极高的恶性肿瘤。由于发病位置特殊，受累器官对生命影响重大，早期诊断率低，预后效果差，其死亡率几乎与发病率一样高。在胆管癌病人中，仅有不到40%的患者能够进行切除手术，但术后极易复发，放疗及化疗对胆管癌又不敏感，因此亟待开发新型的胆管癌诊治方法。 光动力诊断/治疗是近年来发展的诊治肿瘤的新型方法，具有高效、微创、选择性高等优点，前景极为看好。本项目拟在前期基础上，以国外已上市的两个二氢卟吩新药替莫泊芬、他拉泊芬，以及本团队制备的多种新型二氢卟吩光敏剂为研究对象，研究二氢卟吩新药在胆管癌中的荧光成像特点，并从细胞、组织、动物及分子与免疫学水平研究光敏剂抗胆管癌的作用机理，总结胆管癌PDT的关键技术参数，从而建立胆管癌特异性荧光定位诊断与高效的治疗方法；并发现针对胆管癌的具有自主知识产权、高效、靶向候选新药。

胆管癌是一种致死率极高的恶性肿瘤。由于发病位置特殊，受累器官对生命影响重大，早期诊断率低，预后效果差，其死亡率几乎与发病率一样高。在胆管癌病人中，仅有不到40%的患者能够进行切除手术，但术后极易复发，放疗及化疗对胆管癌又不敏感，因此亟待开发新型的胆管癌诊治方法。.光动力诊断/治疗是近年来发展的诊治肿瘤的新型方法，具有高效，微创，选择性高等优点，前景极为看好。.本项目以国外已上市的两个二氢卟吩新药替莫泊芬、他拉泊芬，以及本团队制备的新型二氢卟吩光敏剂为研究对象，对其光化学与光生物学性能进行了研究，测定了新化合物的分布情况及正常组织与肿瘤组织的边界，并在细胞与动物水平研究了激光波长、光敏剂、胆管癌光动力作用之间的关系，研究了作用机理以及定量构效关系，从而发现了1个高效、价廉、无明显毒副作用的光敏新药候选物，提供了胆管癌光动力疗法的关键参数，并建立了光动力诊治胆管癌技术。.项目在研期间，共申请3项国家发明专利；发表论文12篇，其中SCI收录论文4篇，核心期刊论文2篇；培养博士后1名，培养研究生5名。