具有多模成像功能的高强度聚焦超声控制稀土上转换药物智能控释系统的构建及其靶向协同抗肿瘤活性研究

项目名称： 具有多模成像功能的高强度聚焦超声控制稀土上转换药物智能控释系统的构建及其靶向协同抗肿瘤活性研究

项目编号： No.51502284

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 王樱蕙

作者单位： 中国科学院长春应用化学研究所

项目金额： 20万元

中文摘要： 尽管现代医学飞速发展，癌症依旧严重威胁着人类的健康和生命。设计和开发多功能的纳米复合物是实现癌症的早期诊断和治疗的一个新途径。稀土上转换纳米材料(UCNPs)作为一种新型的多功能纳米复合物，在肿瘤的多模式影像诊断和高效治疗的应用基础研究中倍受关注。本项目拟设计构建具有多模成像功能的高强度聚焦超声(HIFU)控制稀土上转换药物智能控释系统，通过简单的调节稀土元素掺杂的种类和浓度，实现单一组份的多功能成像；通过引入靶向的分子和温敏聚合物分子，在高强度聚焦超声控制下实现抗癌药物的定点、定时、定量释放；利用高强度聚焦超声热疗和化学治疗的协同作用，实现低功率、低剂量药物对多种癌细胞的协同杀伤作用，深入探讨HIFU治疗、化疗、两种治疗方式协同治疗的抗肿瘤活性，以及协同治疗作用的机制，为稀土上转换发光纳米材料作为诊疗一体的试剂最终应用于临床提供科学依据。

中文关键词： 稀土上转换纳米材料；多模成像；可控释放；高强度聚焦超声；协同治疗

英文摘要： Despite remarkable advances in modern medical sciences, cancer remains a serious threat for the health and life of human worldwide. Design and develop multifunctional nanomaterials is potential for realizing early diagnosis and treatment of cancer. Lanthanide-doped upconversion nanoparticles have attracted a tremendous amount of attention in the field of multimodality imaging and highly effective therapy. This project will aim at design and construction of high intensity focused ultrasound (HIFU) controlled drug release systems based on upconversion nanocarriers. Adjusting the type and concentration of doping rare earth ions, we can obtain multimodality imaging. After modifying the upconversion nanocarriers with targeted molecules and thermosensitive polymer, the anticancer drugs could be releases at fixed time and place controlled by HIFU. Moreover, we find that HIFU can induce the synergistic effect for killing cancer cells in vitro and in vivo. Based on the obtained experimental results, we will further clarify the synergistic effect mechanism. Our project explores a new avenue to design and construct highly efficient upconversion theranostic agent, which may provide a scientific basis for its application in clinic in the future.

英文关键词： upconversion nanoparticles;multimodality imaging;intelligent controlled drug release ;high intensity focused ultrasound;synergistic therapy