EphA2受体作为胶质瘤新的分子标记物，是免疫毒素治疗胶质瘤的新靶点。我们前期成功构建了靶向EphA2受体的重组免疫毒素EphrinA1-PE38，对胶质瘤具有显著的杀伤作用，但是仍面临免疫毒素难以穿透到肿瘤局部并由此引起的非特异性毒性问题。载药纳米微粒具有一定的靶向性、可缓控释等优点，已成为抗肿瘤药物的良好载体。由此，我们提出载药纳米微粒介导免疫毒素靶向治疗胶质瘤的可能性。我们拟用聚三亚甲基碳酸酯（PTMC）为载体，通过复乳法制备PE38毒素纳米微球，再将导向性EphrinA1片段连接在纳米毒素表面，形成PTMC包裹的靶向纳米免疫毒素EphrinA1-NP/PE38，并研究其理化特征。通过静脉途径给药，观察其对胶质瘤细胞靶向杀伤作用，旨在获得该新型纳米免疫毒素靶向治疗胶质瘤的可靠依据及作用机制。该课题探索新型纳米免疫毒素治疗胶质瘤的新方法，将为免疫毒素靶向治疗肿瘤提供新的思路。

Recent evidence has shown EphA2 as a novel molecular marker and target in glioblastoma multiforme. We have constructed an anti-EphA2 immunotoxin and demonstrated EphrinA1-PE38 have therapeutic efficacy in vitro and in a malignant glioma model. Howerver the failure of location and the nonspecific toxicity remained unresolved.To overcome the limitations, we hypothesize that PE38-loaded anti-EphA2 nanoparticles could target glioma cells. With this in mind, we plan to develope PE38-loaded nanoparticles conjugated with EphrinA1 fragments which bind specifically to EphA2 receptors. Employing PTMC as carriers, we intend to prepare PE38-loaded nanoparticles by double-emulsion evaporation method. The PE38-loaded anti-EphA2 targeted nanoparticles were fabricated by conjugation of EphrinA1 fragments onto the surface of nanoparticles according to carbodiimide method．The ex vivo and in vivo studies will confirmed the therapeutic efficacy and reveal the mechanism of targeted delivery system.This study focus on the novel nanotechnology applied in immunotoxin-based targeted therapy, providing a potentially useful strategy for cancer treatment.