P-gp单抗-USPIO载药纳米颗粒对难治性癫痫的MR分子显像及靶向治疗的研究

项目名称： P-gp单抗-USPIO载药纳米颗粒对难治性癫痫的MR分子显像及靶向治疗的研究

项目编号： No.81201071

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 张军

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 难治性癫痫的发病机制复杂、治疗效果不佳，对常规抗癫痫药物多有耐药性，本课题组前期研究证实其与病灶区脑毛细血管内皮细胞特异性高表达P-gp相关，针对这一主要耐药机制，结合磁共振分子影像、免疫以及纳米技术，制备一种基于P-gp靶向特异性识别的新型磁性微纳米载药分子探针MAb-P-gp-USPIO-AEDs nano-particles（PUNP）。该结构充分利用P-gp单抗对P-gp的特异性识别以及USPIO的超顺磁性，实现病灶靶向早期识别、特异阻断耐药机制、磁共振活体分子显像以及靶向治疗的疗效监测。在BBB模型、癫痫细胞模型及耐药癫痫大鼠模型上通过HPLC、原子力显微镜，透射电镜、免疫电镜、膜片钳技术、磁共振等方法从不同层次进行深入探讨，以期为临床上难治性癫痫耐药机制的早期识别、疗效监测、筛选新药及新型导向性纳米载药系统等研究提供实验基础和理论依据。

中文关键词： 难治性癫痫；磁共振成像；超微超顺磁性氧化铁；P-糖蛋白；

英文摘要： The pathogenesis of refractory epilepsy is complicated, and mostly appears drug resistance to conventional anti-epileptic drugs. Preliminary studies of our group confirmed that P-gp over-expression was higher in refractory epileptic rats，as compared with normal and non-refractory epileptic rat. P-gp was distributed on micro-vascular endothelial cells only in brain，leading to the possibility that P-gp can play as a target molecule for targeted drug delivery against refractory epileptic patients and conjugate a stable nano-particle with P-gpMab on its surface, antiepileptic drugs (AEDs) and superparamagnetic iron oxide ( USPIO) in the core(MAb-P-gp-USPIO-AEDs nano-particles,PUNP) by active targeting on the basis of the unique surface effct of nanoparticles. The structure using P-gp monoclonal antibody on the specific recognition of P-gp, reversible closed role and superparamagnetism, could early identification of targeting lesions, specific blocking mechanisms of resistance, magnetic resonance molecular imaging and targeted therapy in vivo. The study of refractory epilepsy is investigated from different levels in the BBB model cell model of epilepsy, and drug-resistant epilepsy model in rats by HPLC, atomic force microscopy, transmission electron microscopy, immune electron microscopy, patch clamp technique, magne

英文关键词： Refractory epilepsy；MRI；USPIO；P-gp；