基于多肽的诊断治疗一体化纳米材料的制备及其生物医学研究

项目名称： 基于多肽的诊断治疗一体化纳米材料的制备及其生物医学研究

项目编号： No.51473126

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 孙云霞

作者单位： 武汉大学

项目金额： 82万元

中文摘要： 癌症已经成为当今威胁人类生命的一个主要因素，因此，需要一种能有效地诊断和治疗癌症的医疗方法。目前由于生物体内的屏障、药物的非特异性传递、抗药耐药性以及缺乏有效的治疗监测手段等问题，癌症治疗受到了很大的限制。为了克服以上问题，拟设计和制备基于多肽的成像诊断及药物和基因协同治疗的诊断治疗一体化体系。以具有穿膜功能的八聚精氨酸(R8)和内涵体逃逸功能的组氨酸序列（Hn）作为基因载体，以基质金属蛋白酶敏感肽PLGLAG为靶向基团，以抗癌药物阿霉素作为荧光成像基团，分别以BHQ2和金纳米粒子作为阿霉素荧光淬灭剂，构建BHQ2-GPLGLAGR8HnG-DOX和AcCHnR8PLGLAG-DOX/AuNP两类诊疗体系。选取体外性能良好的诊疗材料，将表面过度表达基质金属蛋白酶的肿瘤细胞接种到裸鼠体内培养肿瘤模型，以p53抑癌基因作为治疗基因，重点研究诊疗材料的体内成像及药物和基因协同治疗癌症的效果。

中文关键词： 多肽；成像；诊断；协同治疗；诊疗一体化

英文摘要： Cancer has become a leading factor for threatening to human lives, thus, it is necessary to find an effective therapeutic method to diagnose and therapy cancer. Current cancer therapies are largely limited by biological barriers, non-specific drug delivery, drug resistence of cancer, and lack of an effective method for treatment monitoring. In order to overcome these carriers, series of theranostics materials that combines the modalities of diagnostic imaging and therapy will be synthesized. Two classes of theranostic materials will be prepared based on cell penetrating peptide R8, histidine-rich peptide, MMP-2 activable peptide PLGLAG, and DOX. BHQ2 and AuNP will be respectively used as fluorescence quenching probe to quench the fluorescence of DOX. After these theranostic materials arriving at tumor site, the PLGLAG peptide can be hydrolyzed by the overexpressed MMP-2 protease, leading to the pronounced fluorescence of DOX recovered from quenching to exciting state. And then R8 and Hn can continue carrier DNA to cell and express gene. Hence, the theranostic system is able to induce the cancer imaging and drug/gene synergistic therapy simultaneously.

英文关键词： peptides;imaging;diagnostic;synergetic therapy;theranostics