能同时区分检测多种活性氧分子的聚合物纳米探针研发

研究表明不同的生物活性氧物种（ROS）在诱发、调控某些生理或病理过程中是相互作用、共同促进的，因此对多种ROS分子的同时区分检测意义重大。但由于ROS分子普遍具有反应活性高、半衰期短等特点，开发能同时区分多种ROS分子的荧光探针仍然颇具挑战。本项目拟使用聚甲基丙烯酸甲酯-共甲基丙烯酸（PMMA-MA）包覆多种黑洞猝灭剂（BHQs）构建新型纳米荧光猝灭平台，并优化该纳米平台的荧光猝灭性能和表面修饰方法。设计合成系列具有不同荧光团、能够对不同的ROS分子进行专一检测的小分子荧光探针P1-5，研究P1-5与不同ROS分子的反应性能，优化其分子结构。将优化的探针分子P1-5同时修饰至纳米荧光猝灭平台表面，构建目标纳米探针，并表征其结构。系统测试该纳米探针对多种ROS分子的区分检测性能，研究其对不同药物刺激产生的细胞内源性ROS及小鼠药物性肝损伤（DILI）模型中的ROS分子的区分成像。

Growing evidence has suggested that different reactive oxygen species (ROS) may work together in regulating some important physiological processes as well as in causing some critical illnesses. As a consequence, the simultaneous differentiation of various ROS is of great importance. Unfortunately, the development of fluorescent probes that can simultaneously distinguish various ROS species reminds challenge due to the intrinsic features, such as high reactivity and relatively short half-life time, of most ROS species. In this research project, we try to construct a novel black hole quencher (BHQs)-loaded polymeric nanoquencher platform by using poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA) as the coating matrix. The fluorescence quenching efficiency as well as the surface modification chemistry of this polymeric nanoquencher platform will be optimized. Next, a series of small molecular fluorescent probes, P1-5, which equipped with distinct fluorophores and ROS-specific recognition groups will be rationally designed and synthesized. The sensing properties of P1-5 in response to different reactive oxygen species (ROS) will be investigated. Finally, the optimized small molecular fluorescent probes, P1-5, will decorate to the surface of the above polymeric nanoquencher platform to get the final nanoprobe. This nanoprobe will be characterized by DLS, Zata potential, SEM and TEM, and its sensing properties for simultaneous detection of various ROS will be examined. Significantly, utilizing this nanoprobe to visualize endogenous ROS in living cells or in the liver of drug-induced liver injury (DILI) model mice will be further investigated.