氯毒素靶向聚合物磷脂纳米载体用于脑胶质瘤诊疗一体化研究

项目名称： 氯毒素靶向聚合物磷脂纳米载体用于脑胶质瘤诊疗一体化研究

项目编号： No.81501580

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 郑翠芳

作者单位： 中国科学院深圳先进技术研究院

项目金额： 18万元

中文摘要： 本项目面向肿瘤早期诊断与治疗的重大需求，设计了一种氯毒素靶向的集纳米探针和纳米药物于一体的载体系统并将其用于脑胶质瘤的诊断与治疗的实验研究。这种载体同时负载近红外荧光染料吲哚菁绿(ICG)和化疗药物17-烯丙氨基格尔德霉素(17-AAG)。当该载体携载药物和探针进入体内后，氯毒素能够靶向神经胶质瘤特有的氯离子通道，进而提高探针和药物在肿瘤细胞中的富集浓度，在纳米颗粒富集的肿瘤区域加以近红外激光照射，纳米颗粒内的ICG激发产生高热，通过纳米颗粒内ICG的高热毒性和高浓度化疗药物17-AAG的毒性，共同抑制肿瘤的成长。最终实现纳米载药系统的特异靶向示踪、化学-光热联合治疗的诊疗一体化。我们从细胞和活体两个层面研究该载体系统的靶向性、稳定性、荧光特性、深入研究该纳米载体的药代动力学和抗肿瘤作用机制，为脑胶质瘤的诊断治疗一体化提供可靠的实验依据，为临床脑胶质瘤药物载体的研制提供新的思路和理论依据。

中文关键词： 肿瘤靶向；纳米载体；吲哚菁绿（ICG)；早期诊断

英文摘要： This research project aims to develop a novel nanocarrier system which simultaneous combining nano probe and nano drug in one for the significant demand of tumor early diagnosis and treatment. We developed a chlorotoxin (CTX) targeting polymer lipid nanoparticles which encapsulated anti-tumor drug 17-AAG and near-infrared (NIR) fluorescence dye indocyanine green (ICG) for combining brain glioma diagnosis and treatment. When the vector carrying drug and probe into the body, CTX can be targeted glioma specific chloride channel, which can improve the enrichment probes and drugs in tumor cells. Then use near infrared laser irradiation in the tumor region of nano particle enrichment, ICG in the nanoparticles generate high fever, high fever toxicity of ICG and high concentration of 17-AAG chemotherapy toxicity, mutual inhibition of tumor growth. This system can ultimately realize the specific targeting diagnosis of nanocarrier system and treatment integrated tracer, chemical, thermal combination therapy. We study the vector system from two aspects of cells and in vivo, which include targeting, stability, fluorescence characteristics, pharmacokinetics and anti-tumor mechanism. Such combined strategy will provide reliable experimental basis for the diagnosis and treatment of integration of brain glioma, and provide new ideas and theoretical basis for the development of drug carrier of brain tumor.

英文关键词： Tumor targeted;Nanocarrier;Indocyanine green;Early diagnosis