肿瘤细胞上皮间质转化过程中乏氧与活性氧的近红外荧光检测及其可视化研究

项目名称： 肿瘤细胞上皮间质转化过程中乏氧与活性氧的近红外荧光检测及其可视化研究

项目编号： No.21275092

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： 徐克花

作者单位： 山东师范大学

项目金额： 80万元

中文摘要： 乏氧诱导线粒体活性氧产生，进而参与介导肿瘤细胞上皮间质转化（EMT）过程。本项目基于上转换纳米材料具有光稳定性好、量子效率高、单激发双发射及信号放大、信噪比高等特点，将NaYF4:Yb, Er上转换纳米颗粒与两种有机小分子荧光探针（检测活性氧或者乏氧）通过嵌段共聚物组装，构建一类多肽-聚合物-上转换纳米颗粒-有机小分子探针的复合功能化荧光探针。该类探针会极大提高检测的灵敏度与选择性。另外，拟以具有靶向线粒体功能的亲脂性阳离子染料及对乏氧环境敏感的硝基咪唑类活性基，设计合成线粒体内检测与成像分子氧的近红外荧光探针。实现高选择性、高灵敏度、同时检测乏氧肿瘤细胞内分子氧、信使活性氧的新方法，以及分子氧、活性氧、E-cadherin蛋白（EMT标志性蛋白）的同时成像分析。其结果为乏氧诱导的EMT过程的分子机制研究及其他活性氧介导的信号通路研究提供新的策略与新的途径。

中文关键词： 乏氧；活性氧；硒醇；荧光探针；细胞成像

英文摘要： Mitochondrial reactive oxygen species (ROS) produced by hypoxia can regulate epithelial-mesenchymal transitions (EMT) of tumor cells, but the method to probe endogenous ROS (<nM) has not yet been established. Considering that upconverting nanoparticles (UCNPs) have great advantages in photochemical stability, quantum efficiency, signal-to-noise ratio, and that the fluorescent dye embeded in nano materials has better photochemical stability and higher quantum efficiency, a hybrid functionalized nanoprobe will be designed and assembled, which is composed of polypeptide (cell penetrating peptide or targeted mitochondria peptide), polymer as carrier, UCNPs as energy donors and two dye-based probes as energy acceptors. The assembled nanoprobe should be more sensitive and selective than dye-based probes for O2 and/or ROS, and be more suitable for simultaneously detecting two different target molecules. In addition, a near-infrared fluorescent probe for O2 will be also designed and synthesized with lipophilic cation dye having mitochondria- targeted characteristic and nitroimidazole being a potential hypoxia reporter. Based on these probes mentioned above and an anti-E-cadherin/FITC, it will be very possible to perform simultaneously detecting and imaging O2 and/or E-cadherin and/or ROS produced by hypoxia in the epit

英文关键词： hypoxic；reactive oxygen species；selenol；fluorescent probe；cell imaging