项目名称： 纳米荧光开关的构建及其乳腺癌早期诊断和分期系统建立研究

项目编号： No.31500769

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 洪瑾

作者单位： 中国药科大学

项目金额： 20万元

中文摘要： 乳腺癌的早期发现和诊断，针对不同的分期制定合理的治疗方案是提高其疗效的关键。然而，目前乳腺癌临床早期诊断方法和TNM分期的界定都存在一定缺陷。本项目设计和构建一种在体外处于荧光静息状态，在体内乳腺癌组织和细胞中荧光恢复的“纳米荧光开关”系统。该系统以金纳米粒子作为结构核心和荧光能量转移受体；特异性靶向人表皮生长因子受体的曲妥珠单抗作为靶向配体；乳腺癌细胞（或组织）中金属基质蛋白酶表达水平为肿瘤分期标志。金纳米粒子与有机荧光分子（FITC）通过对金属基质蛋白酶敏感的小肽相连。通过金属基质蛋白酶酶解反应，引发FITC从金纳米粒子表面解离所产生的荧光信号，建立“纳米荧光开关”荧光恢复强度与金属基质蛋白酶表达水平的定量关系。通过对该开关系统深入的机制和定量分析方法研究，以期建立一种新的乳腺癌早期诊断方法和分期系统，并为其他肿瘤的早期诊断提供理论和实践参考。

中文关键词： 纳米荧光开关；乳腺癌；早期诊断；分期；定量关系

英文摘要： Early detection, diagnosis, and a reasonable treatment option for different stages are the key to improve the therapeutic efficacy of breast cancer. However, there are some flaws in the current methods for early diagnosis of breast cancer and defining its TNM stages. In this project, a nanofluorescent switch with a resting state in vitro and fluorescence recovery in breast cancer tissues and cells in vivo is designed and will be constructed. In this system, gold nanoparticles (GNPs) act as a structural core and fluorescence energy transfer acceptor; trastuzumab, specifically targeting the human epidermal growth factor receptor, plays the role of a targeting ligand; the expression levels of MMPs in breast cancer cells (or tissues) is chosen as the staging flag. GNPs and organic fluorescent molecules (FITC) is connected by a matrix metalloproteinase (MMP)-sensitive peptide. With the help of MMPs’ enzyme reaction, FITC fluorescence signal is triggered, which is caused by the dissociation of FITC from the surface of GNPs. The quantitative relationship between the intensity of fluorescence recovery and matrix metalloproteinase expression levels of the nanofluorescent switch is planned to be established. Through in-depth and systematic studies on the mechanism and quantitative analysis method of the switch system, it allows the establishment of a novel method for early diagnosis and staging of breast cancer, and provides theoretical and practical reference for the early diagnosis of other tumors.

英文关键词： nanofluorescent switch;breast cancer;early diagnosis;staging;quantitative relationship