线粒体分子探针设计及其在细胞辨别分析中的应用研究

The incidence of cancer continues to rise in the world, and the early diagnosis of cancer is the keypoint to enhance the survival and cure, the sooner to achieve the diagnosis of cancer, the more hope to completely overcome cancer cells, access to high quality of life. The existing methods of cancer diagnosis are biomarker analysis, imaging diagnosis, pathology, and molecular biology methods. Although the diagnosis of continuous improvement, but the early diagnosis and surgery in the diagnostic method is still relatively lacking. Here we are going to develop a new stratgegy for distinguish cancer cells. Based on the number, shape and function of mitochondria in different states, the fluorescent molecular probes are designed for tagetting the mitochondria in cells. These molecular probes are used to construct the sensor array for identificatio of different cells (normal cells, cancer cells, metastatic cancer cells, etc.). We collect fluorescence intensity and emission wavelength changes and other data. The data is analized by statistical methods to achieve the identification of different cells, mainly to achieve the identification of cancer cells. The ultimate goal is to be able to use the sensor array to achieve the identification of clinical cancer cells, in order to achieve accurate surgical resection of tumor tissue to provide possible methods. Application of the sensor array to identify different cells can reduce the need for molecular probe selectivity, accelerate the development of molecular probes and improve efficiency.

全球恶性肿瘤发病率呈现持续升高态势，因此肿瘤的早期诊断是提升生存期和治愈的关键，越早实现对肿瘤的诊断，越有希望彻底战胜癌细胞，获得高的生存质量。现有的癌症诊断方法主要有生物标志物分析、影像诊断、病理学检查，和分子生物学方法等。虽然诊断方面不断改进，但早期诊断和手术中的诊断方法还是比较欠缺。本项目计划基于不同细胞（正常细胞和癌细胞）中线粒体数量、形态和功能差别，设计合成线粒体靶向荧光探针，应用多个荧光探针组合构建传感阵列，将传感阵列用于不同细胞的线粒体荧光成像，收集荧光强度和发射波长等数据的变化，通过对荧光数据进行数学统计和分析，实现对不同细胞的辨别，重点是实现对癌细胞的辨别，尤其是对临床癌细胞的识别，为实现精确识别肿瘤组织提供新的方法。应用传感阵列识别不同细胞可以降低对分子探针选择性的要求，可以加速分子探针的开发过程，提升效率。

肿瘤的早期诊断是良好预后的关键，现阶段的肿瘤诊断主要有生化分析、影像诊断、病理学检查和分子生物学等方法。虽然诊断技术不断改进，但肿瘤早期诊断仍然面临重要的挑战。本项目发展了新的肿瘤细胞分析方法，解决肿瘤细胞的选择性分析问题。在本项目的支持下完成了荧光分子探针设计合成，构建荧光分子阵列，应用其与不同种类细胞相互作用产生的差异荧光信号，结合仪器分析和数学分析技术，实现细胞的判别分析。合成了具有吲哚盐，吡啶盐，季鏻盐的双电荷结构的系列四苯乙烯衍生物，构建了荧光传感阵列，将传感阵列的荧光输出信号，通过数学分析方法进行处理和主成分分析，实现细胞识别，并通过支持向量机对未知样品进行细胞类型预测，实现了不同种类细胞的辨别分析和预测。在本项目支持下，在复杂肿瘤细胞识别分析、细胞器靶向成像、脑部生物分子成像等方面取得了创新性的成果，相关研究结果发表在Anal. Chem.，Small，Adv. Funct. Mater., Analyst等期刊上。项目实施过程中，共发表研究论文12篇，申请国内专利7项，其中授权专利3项。参加国内外学术会议并做邀请报告，培养的研究生中获得博士学位2人，获得硕士学位8人。