细胞器靶向的细胞微环境双光子荧光探针的设计合成及其在生物成像中的应用研究

项目名称： 细胞器靶向的细胞微环境双光子荧光探针的设计合成及其在生物成像中的应用研究

项目编号： No.21505032

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 毛国江

作者单位： 河南师范大学

项目金额： 21万元

中文摘要： 实时监测细胞器细胞微环境，对研究细胞的生理与病理进程具有重要意义。荧光探针已经成为细胞器细胞微环境监测的有效方法。然而，目前细胞器靶向的细胞微环境荧光探针大多数是基于单光子荧光基团设计的，通常具有激发光波长较短导致的生物样品穿透深度小、光漂白严重、易受到生物体内背景荧光干扰等缺点，在生物成像方面存在一定的局限性。基于双光子荧光探针的生物样品穿透深度大、生物成像背景荧光低、光损伤与光漂白作用小等优点，本项目将双光子荧光探针与细胞器靶向荧光探针相结合，选取生物相关的细胞微环境（pH、粘度）作为研究对象，开发一系列新型的细胞器（高尔基体、内质网、线粒体、溶酶体）靶向的细胞微环境双光子荧光探针，拓展细胞器细胞微环境研究的靶向范围，实现细胞、组织、活体中细胞微环境的动态监测，为细胞器细胞微环境相关的细胞生理与病理进程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。

中文关键词： 荧光探针；双光子；细胞微环境；细胞器；生物成像

英文摘要： Real-time monitoring of intracellular micro-environments in organelles has an important significance to study the physiological and pathological processes in cells. Fluorescent probe has become an effective approach to monitor intracellular micro-environments in organelles. However, most of fluorescent probes for intracellular micro-environments in organelles are based on one-photon fluorophores, which are excited by the excitation source in a rather short excitation wavelength that limits their biological applications because of the shallow penetration depth, strong photobleaching and high autofluorescence in vivo. In this project, due to the advantages of two-photon fluorescent probes such as deeper penetration depth, lower autofluorescence and reduced photodamage and photobleaching in vivo, we attempt to combine it with organelle-targetable fluorescent probes and develop a series of novel organelle-targetable (Golgi apparatus, endoplasmic reticulum, mitochondria and lysosomes) two-photon fluorescent probes for bio-related intracellular micro-environments (pH and viscosity), in order to expand the target organelles for the study on intracellular micro-environments and achieve real-time monitoring of intracellular micro-environments in cells, tissues and animals, which will provide a valuable theoretical basis and technical support for the study on intracellular micro-environments-related physiological and pathological processes and the early diagnosis of intracellular micro-environments-related diseases.

英文关键词： Fluorescent probe;Two-photon;Intracellular micro-environments;Organelle;Bioimaging