细胞器定位的气体信号分子双光子近红外荧光探针的设计合成及生物成像应用研究

Dynamic real-time monitoring of intracellular gaseous signal molecules in organelles is of great significance for investigating their physiological and pathological functions in cells. Currently, several two-photon fluorescent probes have been reported for gaseous signal molecules detection in organelles. These probes adopted two-photon excitation in the near-infrared region. However, their emissions were usually located in the visible light region, limiting the imaging depth and resolution. The combination of the two-photon excitation with the near-infrared emission to construct the two-photon fluorescent probes with near-infrared emission will afford improved imaging effect and imaging depth. In this project, we adopt the Through-Bond Energy Transfer (TBET) strategy, and choose hydrogen sulfide as the model gaseous signal molecule to build a novel two-photon fluorescent probe platform with near-infrared emission. By further modifying with the organelle-targeting groups, a series of novel organelle-targeting (mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome) two-photon near-infrared fluorescent probes will be developed for H2S, which will be applied in dynamic and real-time monitoring of H2S in cells, tissues and animals. Our design may also provide a dye platform for developing two-photon near-infrared fluorescent probes for other gaseous signal molecules. This project will provide a valuable theoretical basis and technical support for the study of physiological and pathological functions of gaseous signal molecules, as well as early diagnosis of related diseases.

动态实时监测细胞器中的气体信号分子对研究其生理病理功能具有十分重要的意义。目前已有一些用于细胞器中气体信号分子检测的双光子荧光探针被报道，这些探针采用处于近红外区的双光子激发，然而其发射大多处于可见光区，成像深度及分辨率均受限。将双光子激发与近红外发射相融合，构建近红外发射的双光子荧光探针能够获得更好的荧光成像效果与成像深度。本项目拟基于跨键能量转移（TBET）策略，以硫化氢作为模型气体信号分子，构建具有近红外发射的双光子荧光探针平台，并将其与细胞器定位的基团相结合，开发一系列新型的细胞器（线粒体、内质网、高尔基体、溶酶体）定位的硫化氢双光子近红外荧光探针，实现细胞、组织、活体中硫化氢的动态实时监测，并为构建其他气体信号分子双光子近红外荧光探针提供染料平台。项目研究成果可望为细胞器内气体信号分子的生理病理功能的研究，以及疾病的早期诊断提供有价值的理论依据和技术支持。

细胞器中的气体信号分子对研究其生理病理功能具有十分重要的意义。本课题通过能量转移策略和合理的分子设计等手段获得了一系列光学性能优越的细胞器靶向的双光子激发的荧光探针，从而实现了细胞、组织、活体中气体信号分子的成像分析。综上所述，此项目为研究细胞器中气体信号分子的生理病理功能奠定了坚实的基础，并为疾病的早期诊断提供了有价值的理论依据和技术支持。项目支助发表SCI论文12篇（一区论文10，二区论文两篇，TOP级5篇），待发表三篇。申请发明专利两项。培养研究生9名。项目投入经费二十万元，支出19.7518万元，各项支出与预算有差别（由于项目获得者从2017年3月从湖南工业大学调离到中南林业科技大学任职），剩余的0.2482万元计划用于本项目研究的后续支出。