线粒体内过氧化氢代谢水平检测的多光子激发的近红外荧光探针研究

As is well known, reactive oxygen species (ROS) play important roles in a number of physiological processes. The excess intracellular ROS may run the risk of disrupting redox homeostasis and giving rise to oxidative stress which is relevant to a variety of pathological processes. Due to the existence of antagonistic biomolecules (such as bio-thiols) and their corresponding enzyme systems, the sub-cellular ROS level is generally in a dynamic procedure. This project is aimed to selectively recognize and monitor H2O2, the key hub molecule in ROS metabolic pathway, and its downstream molecule by designing several series of Ir(III) complexes which are able to target mitochondria and probe the fluctuation of ROS level in monolayer cells and living models by multiple reactions which are ultimately converted to optical signal changes. Combined with multi-photon excitation and NIR emission techniques, these Ir(III) probes hold great promise for early diagnosis of diseases in clinical applications.

活性氧物种(ROS)不仅仅在生物体内多项正常的生理过程中扮演一个重要的角色，还会引起氧化应激，并产生多种病理过程。由于机体内存在与之拮抗的还原性物质（如生物硫醇）与相关的酶系，亚细胞水平分布的ROS经常处在一个动态的波动过程中。本项目瞄准H2O2这种ROS代谢路径中关键的枢纽分子，旨在设计制备几类铱(III)配合物，使其能够满足特异性地在线粒体内利用探针分子的多反应位点所产生的光学信号变化，在单层细胞以及活体模型中，通过多光子激发近红外成像技术、特异性地识别H2O2及其下游分子，监测他们的变化，以进一步反映生物体内ROS代谢的水平，为相关疾病的临床早期诊断提供准确的检测数据。

利用近红外光激发的多光子成像技术，有利于获得以下使其具有诸如：1) 更好的空间分辨率，2)更深的组织穿透成像深度，3)更低的离焦激发/散射影响。同时利用这类激发脉冲光，还可以同时实现多光子磷光寿命/时间门成像，能作为传统荧光成像模式的有力补充，提供细胞微环境的相关信息。而超分辨成像在亚细胞细微结构和细微动态变化的应用中具有其独特的优势。本项目通过配体合理化修饰，设计合成出了可供多光子/超分辨成像的Ir(III)配合物探针，并通过结合波谱学，计算化学，生物化学，生物物理学以及分子生物学等手段研究评判其在各类生物模型中的的应用潜力。累计发表SCI论文3篇(其中一篇收录于Angew. Chem-Int. Ed.)。