新型靶向纳米药物Angio-Ag-NRPMAb的制备及其抑制胶质瘤的机制研究

项目名称： 新型靶向纳米药物Angio-Ag-NRPMAb的制备及其抑制胶质瘤的机制研究

项目编号： No.81471780

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈陆馗

作者单位： 东南大学

项目金额： 72万元

中文摘要： 脑胶质瘤是最常见的颅内原发恶性肿瘤，由于术后复发率高，对放化疗不敏感，故患者的预后极差。文献报道神经纤毛蛋白-1（Neuropilin-1，NRP-1）高表达于胶质瘤细胞，可作为胶质瘤靶向治疗的新靶标。我们前期研究构建了人源抗NRP-1 b1/b2单克隆抗体，证实对胶质瘤增殖、迁移、粘附有抑制效应，但该抗体不易穿透血脑屏障。因此我们拟采用可穿透血脑屏障且靶向脑胶质瘤的Angiopep-2肽修饰银纳米颗粒与抗NRP-1 b1/b2 单克隆抗体化学偶联，制备成Angio-Ag-NRPMAb探针。评价该探针的生物安全性，研究其体内分布规律、穿透血脑屏障的能力、体外/体内靶向抑制胶质瘤效应及相关分子机制，为探索高效靶向治疗脑胶质瘤的新型合成纳米探针提供实验及理论依据。

中文关键词： 纳米探针；靶向治疗；神经纤毛蛋白-1；脑胶质瘤；单克隆抗体

英文摘要： Glioma is the most common primary intracranial malignant tumor with high postoperative recurrent rate. It is hardly sensitive to radiotherapy and chemotherapy.So the prognosis of gliomas is very poor. Neuropilin-1 (NRP-1) is highly expressed in glioma cells, which can be used as a new target for glioma-targeted therapy. In our previous study, the human anti-NRP-1 b1/b2 monoclonal antibody (NRP-1 b1/b2 MAb) was developed and the inhibitory effect of the NRP-1 b1/b2 MAb on gliomas was confirmed. However, the NRP-1 b1/b2 MAb could not be easy to cross the blood-brain barrier. In addition, the preliminary study found that silver nanoparticles have good radiosensitizing effect on tumors. Therefore, we intend to use silver nanoparticles as an assistance for radiotherapy of gliomas. Firstly, we will make silver nanoparticles modified with Angiopep-2 peptide, which is capable of penetrating the blood-brain barrier and targeting gliomas. Then the modified silver nanoparticles will be chemically coupled with the NRP-1 b1/b2 MAb, which results in the development of a new nanoprobe named as Angio-Ag-NRPMAb probe. The in vivo biocompatibility and distribution, the ability to penetrate the blood-brain barrier and target gliomas, the in vitro / in vivo inhibitory effects on gliomas and their molecular mechanisms of the Angio-Ag-NRPMAb probe will be investigated. Our study will provide an experimental basis for the development of a new nanoprobe capable of penetrating the blood-brain barrier, radiosensitizing, and attaining the collaborative targeted therapy of gliomas.

英文关键词： nanoprobes;targeted therapy;Neuropilin-1;brain glioma;monoclonal antibody