线粒体靶向竹红菌素光动力治疗脉络膜新生血管的实验研究

Choroidal neovascularization is the leading cause of irreversible blindness.Photodynamic therapy is the successful therapeutic method, but verteporfin is the only available photosensitizer for CNV approved by FDA and its treatment cost is so expensive that the patients in our country could not afford it.Hypocrellin B (HB)first developed in China and is known for its high photosensitization but very low dark toxicity and low cost.Our previous studies demonstrated that they could occlude microvascular and we also synthesized nano-lipsomal HB.Since liposomal HB can not provide target therapy and neovascular endothelial cells have abundent mitochondria, the aim in this study is to synthesize nano-liposomes delivered hypocrellin B targeting mitochondria and induce cell apoptosis by mitochondrial path. Further, we will study the photodynamic effect of mitochondria-targeted liposomal HB on CNV and determine the relationship of drug or light dose-effect. The last purpose is to study the mechanism of vascular endothelial apoptosis in HB-PDT. This study will make us fully play resouce advantage and will benefit to the CNV patients who could not afford the current PDT　in our county. And it also has guiding significance and scientific values to establish a new therapeutic direction of mitochondria-targeted liposomes on CNV.

脉络膜新生血管（CNV）是不可逆性盲的重要致病原因。光动力疗法（PDT）虽为首选治疗方法，但面临唯一可用的光敏剂价格昂贵、国人无法承受的窘境。竹红菌乙素（HB）是我国特有的天然光敏剂，具有光毒性高、副作用小且成本低等优点，我们前期已证实HB可以很好封闭微血管，并构建了HB纳米脂质体，但无法靶向定位。本项目拟利用纳米脂质体易于修饰的优势，结合新生血管内皮细胞线粒体含量极为丰富的特点，构建线粒体靶向HB纳米脂质体，最大效率启动占据凋亡核心地位的线粒体途径，以提高PDT对内皮细胞的杀伤效率和靶向性；进而系统研究其对CNV模型的封闭效应，确定量效关系；初步探索诱导血管内皮细胞凋亡的分子机制。该项目不仅可以最大限度地发挥我国的资源优势，对于改变我国CNV患者无"药"可医的现状具有重大的科学意义，而且靶向特定细胞器提高PDT治疗效率的思路对于开辟一个全新的CNV治疗方向具有重要的指导意义和科学价值。