铼-188-n(BSA)-VEGI-FA复合纳米靶向载药体系的构建及协同杀伤肿瘤细胞的实验研究

肿瘤的生长、局部浸润与转移均依赖于新生血管的形成，抗血管生长治疗是目前肿瘤生物治疗研究领域的热点之一。然而，目前的抗血管生长制剂存在靶向性差、病灶部位浓度低及毒副作用大等缺陷。本项目拟构建以血管内皮生长因子VEGI和叶酸为靶向分子的白蛋白纳米胶囊载运体系，并对其进行治疗核素铼-188的标记，获得一种新型放射性纳米靶向药物188Re-n (BSA)-VEGI-FA。蛋白纳米胶囊介导的肿瘤靶向给药及双靶点的特性，改善体内药代动力学行为，提高药物在靶区的浓度及亲和力，同时铼-188对肿瘤血管内皮细胞和肿瘤细胞的内照射可诱发细胞凋亡。这种协同杀伤肿瘤的机制可以最小剂量的药物达到诱发肿瘤消退的目标。本项目的顺利实施不仅能为现代肿瘤治疗开辟新的思路，而且将为研发多靶向抗肿瘤新生血管的放射性纳米药物探索实验基础。

The whole process of tumor growth, local infiltration and metastasis depend on the generation of new blood vessels. Anti-angiogenesis is one of the most hotspots in the field of tumor biological therapy. However, those agents used in pre-clinic have some defects such as poor targeting property, low concentration in the focal areas and side effects. In this project, we intend to build a novel nanoparticle capsule carrying system, which is surface introduced by VEGI and FA. We radiolabel this system with 188Re further, to get a new radiopharmaceutical, 188Re-n( BSA)-VEGI-FA, which conjugated two target molecules and a therapeutic radionuclide. The application of protein nano-capsulation and two targeting molecules mediated the delivery characteristics in vivo and improved the drug concentration and affinity in the target area. At the same time, 188Re induced apoptosis of tumor vascular endothelial cell and tumor cells by the internal radiation effect. This synergy mechanism needs relatively small doses drug to achieve the purpose of killing the tumor cells. This project not only opened up new ideas for modern tumor treatment, but also explored experimental basis to develop more anti-tumor vascular drugs.