荧光共振能量转移介导的荧光探针用于溶酶体pH成像检测的研究

溶酶体参与细胞吞噬、凋亡以及癌症发展等过程。溶酶体的这些生理功能与溶酶体的pH密切相关，检测/监测细胞内pH的动态变化对于了解溶酶体的众多生理效应、作用机制等有着重要的意义。因此，发展低背景的、能灵敏检测溶酶体酸度以及标记溶酶体形态与位置的荧光探针技术对研究与溶酶体相关的细胞信号传导以及癌症诊断等有重要的意义。本项目通过自主设计合成的荧光探针，构建基于荧光共振能量转移的比率方法，实现溶酶体内pH的检测。项目研究成果将有助于丰富pH荧光探针的内容，同时也有助于发展利用比率荧光探针测量细胞信号传导中溶酶体酸度变化的简捷方法，为研究细胞内pH 变化调节的生物信号传导提供一种有效研究手段。

The acidity of lysosomes is essential for a variety of biological functions ranging from autophagy to apoptosis, etc. Aberrant alterations of the lysosomal pH have been implicated in many pathological events, e.g. cancer metastasis, providing motivations to develop noninvasive and accurate methods for imaging of lysosomal pH. Low background and selective staining of lysosomes with pH probes have attracted considerable attention. This project mainly focouses on construction of the new ratiometic fluorescent probes based on fluorescence resonance energy transfer (FRET) to realise the detection of pH in lysosome. The results will not only greatly enrich the development of pH probes, but also suggest the potential utility for studies of lysosome-involved cell biology or evaluation of lysosome-targeted cancer therapy.