新型可逆乏氧荧光探针的设计与合成及其在肿瘤细胞中的成像研究

项目名称： 新型可逆乏氧荧光探针的设计与合成及其在肿瘤细胞中的成像研究

项目编号： No.21202097

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机化学

项目作者： 崔雷

作者单位： 上海理工大学

项目金额： 25万元

中文摘要： 肿瘤的氧合状态是放疗、化疗、生物治疗、加热等治疗的重要影响因素。肿瘤乏氧细胞对放射治疗的敏感性低，对化疗、生物治疗等同样具有耐受性。乏氧荧光成像作为一种无创伤、全面、可重复的乏氧探测方法不仅能准确评价肿瘤细胞内部氧分压水平，判断其恶性程度及转移倾向性，还可作为前瞻性判断治疗敏感性和预后的重要独立预测因子，有助于临床治疗计划的制定，从而针对病人选择个性化的治疗方案。本项目首次提出可逆乏氧荧光探针的设计方案。充分利用肿瘤细胞中乏氧区域和正常区域甚至正常细胞中较大的氧化还原电位差异，及在生物温和条件下发生可逆氧化还原反应的官能团的基础上设计出了可逆乏氧荧光探针。为了更好的应用于生物及活体，选用近红外区的花菁染料为荧光团，可以对癌症患者的临床诊断及个性化治疗提供更好的判断依据和解决方案。

中文关键词： 荧光；乏氧；肿瘤；可逆；

英文摘要： Tumor Oxygenation Status tampers the therapeutic effects of radiotherapy, chemotherapy, biotherapy and thermotherapy. Tumor hypoxic cells not only show low sensitivity to radiotherapy, but also resist to chemotherapy and biotherapy. Hypoxia fluorescent imaging is a noninvasive, comprehensive and repeatable detect manner that could correctly evaluate the oxygen lever in tumor in order to evaluate its malignant degree and metastasis, also could be used as independent prognostic factor to evaluate the therapeutic sensitivity and prognosis. It is helpful for the establishment of clinical therapeutic plan and the patient-oriented individual therapeutic plan. In this project, we proposed for the first time the design of reversible fluorescent probes for hypoxia, which fully utilized the major oxidation-reduction potential difference between tumor hypoxic cells and normal cells, based on the function groups that could be oxidized and reduced under mild biological environment. Furthermore, in order to make better evaluation performance on the clinical diagnosis and individual therapeutic, near infrared cyanine dye th was chosen as fluorophore, which is suitable for in-vivo test.

英文关键词： fluorescence；hypoxia；tumor；revisible；