生物肽标载磁性药物微粒对脑胶质瘤靶向治疗的应用基础研究

项目名称： 生物肽标载磁性药物微粒对脑胶质瘤靶向治疗的应用基础研究

项目编号： No.81201992

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 赵明

作者单位： 中国人民解放军总医院

项目金额： 23万元

中文摘要： 脑胶质瘤占颅内肿瘤的40%。即使接受手术联合放化疗的综合治疗，60%以上患者生存期不超过1年。几十年来化疗对于改善患者预后始终效果不佳，缘于全身注射药物后肿瘤局部无法达到有效杀伤浓度，这成为脑胶质瘤化疗中难以攻克的难题之一，长期无明显突破。针对这一问题，本研究拟制作HIV-1 tat跨膜肽标载磁性药物微粒，先检测其物理化学特性，之后利用荧光/共聚焦显微镜、细胞毒性试验和流式细胞技术观察其对胶质瘤的入胞作用和生物毒性，然后通过核素成像、高效液相色谱分析、生存分析和病理组织学方法，检测在外磁场靶向下磁性药物微粒对脑间质和肿瘤细胞内药物浓度的提高作用，以及对荷瘤大鼠生存期的影响。本项目拟联用磁靶向和生物靶向作用提高脑胶质瘤内的药物浓度，解决全身给药后脑胶质瘤内药物浓度过低、治疗效果差的问题，以期为脑胶质瘤的化疗提供一种高效安全的新方法。

中文关键词： 磁靶向；纳米；化疗；；

英文摘要： Glioma accounts for more than 40% brain tumors. Survival time of the patients does not exceed 1 year in more than 60% patients even after consecutive surgery, radiotherapy and chemotherapy. Chemotherapy has been playing little role in improving the survival of patients because the local drug concentration is very limited after general administration. To solve the problem, this research is to manufacture HIV-1 tat labeled magnetic drug nanoparticles and test their physical and chemical features. Fluorescence/confocal microscopy, cytotoxicity tests and flow cytometry are used to observe their endocytosis and biotoxicity against glioma. Afterwards radio-imaging, high performance liquid chromatography, survival analysis and histopathology analysis are performed to evaluate the improvement of the interstitial intra/extra-cellular drug concentration and survival of glioma-bearing rats. This research aims to elevate intra-glioma drug concentration by magnetic and biological targeting to prevent low local drug concentration after systematic administration and poor chemotherapeutic effects, in order to provide an efficient and safe method for glioma chemotherapy.

英文关键词： magnetic targeting；nano；chemotherapy；；