Wang Qianqian, Zhou Liyi, Qiu Liping, Lu Danqing, Wu Yongxiang, Zhang Xiao-Bing
Molecular Sciences and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, PR China.
Analyst. 2015 Aug 21;140(16):5563-9. doi: 10.1039/c5an00683j.
Lysosomes are acidic organelles (approximately pH 4.5-5.5) and tracking the changes in lysosomal pH is of great biological importance. To address this issue, quite a few of fluorescent probes have been developed. However, few of these probes can realize the tracking of dynamic changes in lysosomal pH. Herein, we report a new lysosome-targeted ratiometric fluorescent probe (FR-Lys) by hybridizing morpholine with a xanthane derivative and an o-hydroxy benzoxazole group. In this probe, the morpholine group serves as a targeting unit for lysosome, the xanthane derivative exhibits a pH-modulated open/close reaction of the spirocycle, while the o-hydroxy benzoxazole moiety shows a pH modulated excited-state intramolecular proton transfer (ESIPT) process. Such a design affords the probe a ratiometric fluorescence response towards pH with pH values ranging from 4.0 to 6.3. The response of the probe to pH was fast and reversible with high selectivity. Moreover, this probe possesses further advantages such as easy synthesis, high photostability and low cytotoxicity. These features are favorable for tracking dynamic pH changes in biosystems. It was then applied for dynamic imaging pH changes in lysosomes with satisfactory results.
溶酶体是酸性细胞器（pH约为4.5 - 5.5），追踪溶酶体pH值的变化具有重要的生物学意义。为了解决这个问题，已经开发了不少荧光探针。然而，这些探针中很少能实现对溶酶体pH动态变化的追踪。在此，我们报道了一种通过将吗啉与呫吨衍生物和邻羟基苯并恶唑基团杂交而设计的新型溶酶体靶向比率荧光探针（FR-Lys）。在该探针中，吗啉基团作为溶酶体的靶向单元，呫吨衍生物表现出螺环的pH调节开/关反应，而邻羟基苯并恶唑部分显示出pH调节的激发态分子内质子转移（ESIPT）过程。这种设计使探针在pH值为4.0至6.3范围内对pH具有比率荧光响应。探针对pH的响应快速且可逆，具有高选择性。此外，该探针还具有合成简便、高光稳定性和低细胞毒性等优点。这些特性有利于追踪生物系统中的动态pH变化。随后将其应用于溶酶体中pH变化的动态成像，结果令人满意。
