组织因子靶向纳米粒介导光化学梗塞法治疗实体霍奇金淋巴瘤的实验研究

与正常血管不同，很多实体瘤与血液恶性肿瘤的血管内皮均高表达组织因子（TF），其可作为针对肿瘤血管的特异性靶点。在前期研究中，本课题组根据FⅦ与TF特异性结合的空间结构，原核表达、制备了EGFP-EGF1融合蛋白，并将其与PEG-PLGA纳米粒共价结合制备了EGF1-EGFP-NP，体内外实验均证实其具有良好的TF靶向性和生物安全性。玫瑰红是一种光敏剂，静脉注射后可经局部冷光照射产生活性氧损伤血管内皮，导致TF释放和血栓形成。由于玫瑰红的体内分布缺乏特异性，本研究计划将玫瑰红包载在EGF1-EGFP-NP内部，静脉给药后通过TF靶向性聚集到高表达TF的肿瘤血管，然后采用冷光对肿瘤定位照射，局部产生的氧自由基可损伤肿瘤血管内皮导致TF进一步释放，既可提供靶标募集更多纳米粒子，又可持续产生TF激活凝血瀑布，导致目标部位血管梗塞，中断肿瘤细胞血液供应，可期望为实体肿瘤的治疗提供新的思路。

As TF is overexpressed on many cancer in solid tumors，newly formed tumor capillary blood vessels distribute many TF because they lack tight junctions between endothelial cells.EGFP-EGF1 protein-conjugated PEG-PLGA nanoparticles, recently developed in our laboratory,have shown thrombus targeting property by advantage of theTF-targeting property of EGFP-EGF1 fusion protein in vivo and in vitro. Rose bengal is a kind of photosensitizer.Upon exposure to illumination of appropriate wavelengths, which react with molecular oxygen in the surroundings, generating reactive oxygen, damaging the endothelium and inducing TF overexpression, finally thrombosis. However,it's half time is limited and is of toxicity. Rose will be encapsulated in the EGFP-EGF1 fusion protein conjugated PLGA nanoparticles and targeting TF on tumor vessels, and then the tumors will be illuminated at appropriate wavelength.Activated oxygen will damage the endothelium and induce more and more TF expression. So many TF will not only become the target of the nanoparticles, but also activate the blood coagulation and starve the tumor cells, which will be a promising choice for many other solid tumors.