线粒体靶向的磁性纳米药物载体的构建及其在癌症治疗中应用

项目名称： 线粒体靶向的磁性纳米药物载体的构建及其在癌症治疗中应用

项目编号： No.51272002

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 毕红

作者单位： 安徽大学

项目金额： 80万元

中文摘要： 常用的癌症化疗药物存在药效低、副作用大等缺点。最新研究表明这些化疗药物可能是通过"线粒体启动效应"(mitochondria priming)导致癌细胞死亡的。因而线粒体靶向的纳米载体具有选择性高、疗效好、毒副作用小等优势。然而，目前以脂质体为核心的纳米载药系統存在明显的缺陷，构建高效低毒的线粒体靶向纳米载体仍是一个亟待解决的难题。本项目拟对一维磁性纳米线表面进行修饰，使其表面带有巯基和羧基，再通过巯基与线粒体靶向的三苯基膦阳离子以二硫键相连，同时利用羧基与抗癌模型药物阿霉素结合，由此构建一种兼具线粒体靶向和磁靶向双重功能的纳米载体。该纳米载药系统不仅能靶向细胞线粒体并释放出药物进入线粒体内，而且在外加磁场下能将药物输运至老鼠体内的肝癌病灶部位富集，杀死癌细胞。此系统可提高药效，减少化疗药物对正常组织和器官的损害。该研究为构筑新一代用于癌症治疗的靶向细胞器的纳米药物载体提供了一条有益途径。

中文关键词： 线粒体靶向；纳米载体；磁性；癌症治疗；碳量子点

英文摘要： There are notable disadvantages of commonly-used chemotherapy drugs such as low drug efficiency and severe side effects. Recently, it has been demonstrated that these anticancer drugs may kill cancer cells via a mitochondria- primed cell death mechanism. Therefore, specific mitochondria-targeted nanocarriers possess many advantages such as high selectivity, good therapy effect and low toxicity. However, the present liposome-based nanodelivery system has obvious drawbacks, it is still a great difficulty to design and prepare an ideal mitochondria-targeted nanocarrier. Our project aims at constructing a novel kind of both mitochondria-targeted and magnetic-targeted nanocarrier by surface modification of magnetic nanowires to attach thiol(-SH) and carboxyl(-COOH) groups, and then triphenylphosphonium (TPP) cation can be linked to the nanowire surface via a degradable disulfide bond while the anti-tumor drug doxorubicin (DOX) can be attached to the nanowire by bonding with carboxyl group. The loaded model drug DOX will be released from the mitochondria-targeted nanocarrier and then delivered directly into the mitochondria inside the liver tumor cells. Moreover, under an external applied magnetic field, the loaded drug on this bifunctional nanocarrier will be focused on the liver tumor area in a mouse and then kill

英文关键词： mitochondria targeted；nanocarrier；magnetic；cancer therapy；carbon quantum dots