光动力学疗法中单态氧的产生机制研究

Photodynamic therapy (PDT) is an emerging treatment modality, which uses light, oxygen and photosensitizer. It can be used for curative and palliative treatment of a variety of malignant and non-malignant diseases. At present, PDT has been considerated as the fourth non-invasive treatment modality for tumor besides the tranditional modalites of surgery, radiatherapy and chemotherapy. The success of PDT mainly depends on the photosensitizer and the amount administered, the drug-light interval, delivered light and available molecular oxygen in the treatment site. To date, the major cytotoxic species with most current photosensitizers in PDT is believed to be the singlet oxygen. However, the mechanism studies of singlet oxygen generation during PDT are very limited due to the lack of available and high-sensitive monitoring techniques. This project proposes to design, consturct and test a novel singlet oxygen luminesncence imaging system with a newly available NIR-CCD. With the development of time-resolved and spatially-resolved singlet oxygen luminescence systems, the influence of the delivered photosensitizer and light, molecular oxygen, and the tissue optical properties on the amount and distribution of the photosensitized singlet oxygen generation will be quantitatively evaluated, which aiming at the exploration of the natural mechanisms of singlet oxygen generation during PDT treatment at molecular levels. This project could dramatically expand our knowledge of singlet oxygen behaviors in biology and medicine, which is extremely useful for optimizing the treatment protocols and enhancing the clinical PDT efficiency.

光动力学疗法（Photodynamic Therapy，PDT）已逐渐成为继手术、放疗和化疗之外治疗肿瘤的第四种微创疗法。光敏剂、光和氧分子是PDT的三个基本要素。单态氧作为PDT的主要细胞毒性物质，它的产量除了取决于靶组织中潴留的光敏剂浓度和照光剂量之外，实际上还与光敏剂的类型（光敏剂的三重态寿命和单态氧量子产率），组织体中的氧含量，以及组织体的光学特性等密切相关。截至目前，PDT中有关单态氧产生机制的实验研究相对匮乏，其根本原因在于缺少有效的研究手段。项目拟在开发具有荧光和氧含量监测功能单态氧发光检测系统的同时，开发高灵敏度的单态氧发光成像系统。通过实验研究阐明PDT中光敏剂剂量、光剂量、氧含量和组织光学特性等参量对单态氧产量与空间分布的定量影响，揭示单态氧的产生机制。项目研究不仅有助于优化临床治疗方案，而且还可为构建PDT剂量学及其临床应用推广奠定理论基础，有望获得创新性研究成果。

单线态氧作为光动力疗法（PDT）的主要生物毒性物质，其产量不仅取决于靶组织中潴留的光敏剂浓度和照光剂量之外，还取决于光敏剂的类型（光敏剂的三重态寿命和单态氧量子产率），组织体中的氧含量，以及组织体的光学特性等。本项目开发了具有荧光和氧含量监测功能单线态氧发光检测系统和高灵敏度的单线态氧发光成像系统，实验定量研究了PDT中光敏剂剂量、光剂量、氧含量和组织光学特性等参量对单线态氧产量的影响。此外，首次实现了活体动物模型中单线态氧发光的实时成像，并利用漫反射光谱定量检测光敏化过程中的血氧饱和度。相关研究结果为优化临床PDT治疗方案和构建剂量评估方法提供了理论基础。