肺癌早期诊断用高精准靶向型磁共振造影复合纳米粒子的研究

项目名称： 肺癌早期诊断用高精准靶向型磁共振造影复合纳米粒子的研究

项目编号： No.51203175

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 沈折玉

作者单位： 中国科学院宁波材料技术与工程研究所

项目金额： 25万元

中文摘要： 为实现对肺癌的早期诊断，本课题拟开发一种高精准靶向型磁共振造影复合纳米粒子，研究思路如下：构建并制备出尺寸小于200 nm、内部包埋有磁共振造影剂、表面偶联有配体叶酸并接枝有pH敏感型高分子的可生物降解磁共振造影复合纳米粒子，使复合纳米粒子表面的叶酸在正常生理条件下隐藏在高分子之中、在肺癌组织环境下由于高分子收缩而暴露出来与肺癌细胞表面的叶酸受体发生特异性相互作用，达到降低正常细胞对复合纳米粒子非特异性摄取的目的；通过医学磁共振成像技术，研究该复合纳米粒子在肺癌组织内的磁共振造影信号增强机制；研究复合纳米粒子表面pH敏感型高分子的接枝密度和链长长度对靶向造影效果的影响，优化高分子的接枝密度和链长长度，有效提高磁共振造影复合纳米粒子对肺癌组织的靶向效果。通过本项目的研究，有望制备出一种能高精准靶向肺癌组织的磁共振造影复合纳米粒子，为将来发展一套特异、灵敏的肺癌早期诊断技术打下基础。

中文关键词： 肺癌；早期诊断；高精准靶向；复合纳米粒子；磁共振造影剂

英文摘要： This project aims to develop novel high-specifically-targetable composite nanoparticles with magnetic resonance imaging (MRI) contrast agents inside for detection of lung cancer in early stage, including preparation of sub-200 nm biodegradable nanoparticles, encapsulation of MRI contrast agents inside the nanoparticles, conjugation of ligand folic acid and graft of pH-sensitive polymers on the surface of the nanoparticles. In surroundings of normal cells, the ligand folic acid on the surface of the composite nanoparticles is always hidden in the pH-sensitive polymers. However, after arriving at lung tumour site, the folic acid will be exposed to recognize and bind to folate receptors on the surface of lung cancer cells due to shrinkage of the pH-sensitive polymers. This smart system is high selective and able to distinguish the molecular signatures of lung cancer cells without non-specific uptake by trillions of healthy cells in the body. This project will also investigate the MRI signal enhancement mechanism of the composite nanoparticles in the lung tumour site; optimize the length and density of the grafted pH-sensitive polymers on the surface of the composite nanoparticles by analysing the in vivo MRI efficacies, improve the lung tumor targetability of the composite nanoparticles. The expected results of thi

英文关键词： lung cancer；early diagnosis；high-specifically-targetable；composite nanoparticles；MRI contrast agents