Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China.
School of Pharmacy, Anhui Medical University, Hefei, 230032, China.
Anal Chim Acta. 2021 Dec 1;1187:339146. doi: 10.1016/j.aca.2021.339146. Epub 2021 Oct 5.
Mitophagy, a specialized form of autophagy, holds the key to cellular metabolism and physiology. Viscosity is a significant marker for visualization of the mitophagy process in real-time. Hence, development of well-performing viscosity probe is beneficial to study mitophagy-related dynamic physiological and pathological processes. Here, a new strategy was proposed by combination of AIE property and molecular rotors to design novel viscosity probe. The probe named TPA-Py was obtained by Knoevenagel condensation reaction of AIE unit and pyridine salt, which giving the probe excellent near-infrared emission, good water-solubility and mitochondrial targeting ability. Most importantly, TPA-Py owns two rotatable parts of triphenylamine and double bond, enabling the probe to equip with AIE property and sensitive recognition units for viscosity. With the environmental viscosity increasing, the rotation of the molecular rotor and the AIE unit is restricted effectively, the probe displayed strong fluorescence. Then, TPA-Py was successfully employed for monitoring the mitophagy process in A549 cells by imaging viscosity alterations. As mitophagy constitutes an important consideration in the pathogenesis of drug-induced liver injury, TPA-Py was also applied to explore the variation of viscosity in production and remediation pathways of APAP-induced liver injury. These results demonstrated that TPA-Py was a highly sensitive viscosity probe which holds great potential of biological applications.
自噬是一种特殊的细胞自我降解过程,对细胞代谢和生理功能至关重要。黏度是实时可视化自噬过程的重要标记物。因此,开发性能良好的黏度探针有助于研究与自噬相关的动态生理和病理过程。本研究提出了一种将聚集诱导发光(AIE)特性和分子转子结合的新策略,用于设计新型黏度探针。通过 AIE 单元和吡啶盐的克脑文格尔缩合反应得到了探针 TPA-Py,该探针具有优异的近红外发射、良好的水溶性和线粒体靶向能力。重要的是,TPA-Py 拥有两个可旋转的三苯胺和双键部分,使探针具有 AIE 特性和对黏度的敏感识别单元。随着环境黏度的增加,分子转子和 AIE 单元的旋转受到有效限制,探针显示出强荧光。然后,通过成像黏度变化,TPA-Py 成功用于监测 A549 细胞中的自噬过程。由于自噬在药物性肝损伤的发病机制中是一个重要的考虑因素,TPA-Py 也被应用于研究 APAP 诱导的肝损伤产生和修复途径中的黏度变化。这些结果表明,TPA-Py 是一种高灵敏度的黏度探针,具有很大的生物学应用潜力。