荧光信号释放受分子逻辑门机制控制的新型靶向智能探针及荧光标记成像

项目名称： 荧光信号释放受分子逻辑门机制控制的新型靶向智能探针及荧光标记成像

项目编号： No.21272172

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 曾宪顺

作者单位： 天津理工大学

项目金额： 80万元

中文摘要： 围绕开发量子效率高、标记特异性强，光学标记后可从健康组织中高灵敏、高选择性的区分出肿瘤组织的荧光探针。本项目拟利用健康组织和肿瘤组织的生理pH值差异，从探针①满足靶向选择性标记功能；②荧光信号报告基团由细胞活性物质激活和③光学信号释放受细胞pH值控制这三个基本要素切入，在探针的设计方面充分利用抗体-受体结合原理对探针进行靶向修饰来实现对肿瘤细胞光学标记的一级选择性；同时，利用细胞活性物激活探针的光学信号报告基团和细胞pH调控光学信号释放这两种细胞内分子激活事件来控制光学信号到达二级选择性的目的，设计出荧光探针在细胞内激活和光学信号释放受类似AND逻辑门输入机制控制的新型靶向智能荧光探针。通过这类探针对肿瘤模型的光学标记成像研究，获得肿瘤-本底光学信号对比度高和成像清晰度高的荧光标记检测模型，发展从健康组织中区分出肿瘤组织的新型智能荧光探针标记技术,并建立对肿瘤进行荧光标记成像检测新模型。

中文关键词： 近红外荧光染料；荧光探针；氧化活性物种；荧光成像；细胞器靶向选择性探针

英文摘要： 1. Molecular Design of the Smart Bioprobes with High Selectivity and Sensitivity. To obtain novel tumor targeting bioprobes for labelling and fluorescence optical imaging with high selectivity and sensitivity, this project will focus our efforts on the molecular design of smart fluorescence bioprobes by taking advantage of the cellular pH differences between health tissue and tumor. Our strategy is taking the following three important factors into account for the molecular design of the bioprobes to endue them with smart natures. Namely, the specific labelling of tumors is achieved by modification of the bioprobes by arginine-glycine-aspartic acid (RGD) (or octreotide) peptide according to the antibody- antigens binding mould; the signal silence fluorescence reporters are activable by the reactive high oxygen species (rHOS) in cells; and the signal release of the activated bioprobes is controlled by cellular pH value. 2. Specific Labeling, the Activation of the Reporter and the Optical Signal Release of the Activated Reporter. Firstly, the bioprobes are accumulated selectively on the membrane of tumor cells by using an integrin (or somatostatin) targeted strategy by the moiety of RGD (or octreotide) peptide within the bioprobes. After the bioprobes being endocytosed by cells, the signal silence fluorescence

英文关键词： Near-infrared fluorescence dye；fluorescence bioprobe；reactive oxygen species；fluorescence bioimaging；organelles-targeting probe