双靶向多靶点纳米放疗增敏剂的构建及其增敏放射治疗脑胶质瘤的研究

脑胶质瘤是颅内最常见的难治性恶性肿瘤，术后放疗是重要的治疗手段，但因血脑屏障的存在和胶质瘤细胞对射线的不敏感，放疗效果不好。前期研究发现，将放疗增敏剂制备成纳米前药可以克服上述问题，有效地增敏脑胶质瘤的放射治疗，该结果发表于Biomaterials（IF 8.3）。在此基础上，本项目预合成和制备“靶向血脑屏障和靶向脑胶质瘤”双靶向修饰的PEG2000-Poly-Lys-PMTZ（含有阳离子聚合物的Poly-Lys和具有聚甲硝唑的PMTZ乏氧细胞增敏剂）前药纳米载体，递送抑制DNA修复能力来增敏肿瘤细胞的Dbait分子和将细胞周期阻滞在放射敏感的G2/M期来增加放疗敏感性的紫杉醇，实现双靶向、多靶点纳米放疗增敏剂增敏脑胶质瘤放射治疗，有效的杀死脑胶质瘤。预实验已经完成部分材料的合成。本研究的如期完成，将为临床放射治疗脑胶质瘤提供有应用价值的纳米放疗增敏剂，提高放射治疗效果。

Glioma is the most common intracranial tumor, threatening human health and life. Radiation therapy played an important role in treatment of glioma after surgery. Irradiation of glioma has little effect, due to the presence of blood brain barrier and its resistant to radiation. In previous studies, we have demonstrated that a hypoxic radiosensitizer-prodrug nanoparticle can overcome these problems and increase radiosensitivity of glioma. The result was published on Biomaterials (IF 8.3). In this study, we prepared a PEG2000-Ploy-Lys-PMTZ prodrug nanocarrier with blood brain barrier and glioma targets, which contained hypoxic radiosensitizer nitroimidazoles, to deliver DNA repair inhibitor Dbait and arrest cell cycle in G2/M to sensitive radiation paclitaxel to increase radiosensitivity of glioma. Before formal experiment, a portion of material was synthesized. Our expected results will provide a multitargeted nano-radiosensitization for clinical radiotherapy application and improve the effect of radiotherapy on glioma.