An AIE-TICT fluorescence probe cascade responsive to H2S, polarity and viscosity to track microenvironment changes in cellular model of ischemia-reperfusion injury

Abstract

Background: Ischemia-reperfusion injury is a common cause of cardiovascular and cerebrovascular diseases. The reoxygenation during reperfusion leads to an overproduction of reactive oxygen species (ROS). As an antioxidant, H₂S can scavenge ROS to inhibit oxidative stress and inflammatory reaction, thus attenuating ischemia-reperfusion injury. In this process, the changes of cellular microenvironment (polarity or viscosity) have not been fully discussed. In order to real-time track the changes of cellular microenvironment during the treatment of ischemia-reperfusion injury with H₂S. It is necessary to develop highly selective and sensitive probes that can cascade response to hydrogen sulfide and cellular microenvironment.

Results: We designed and synthesized a fluorescent probe TPEC-DNBS which can produce cascade response to H₂S and microenvironment. An intermediate TPEC-OH is produced after highly selective and sensitive response to H₂S, which can further respond to polarity and viscosity. In addition, due to the aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) effects, polarity can promote the fluorescence emission wavelength and intensity of TPEC-OH to produce double response characteristics, and its change trend (from weak green fluorescence at low polarity to strong red fluorescence at high polarity) is opposite to that of traditional polar probes (from strong green fluorescence at low polarity to weak red fluorescence at high polarity). Viscosity can only induce the change of fluorescence intensity. By constructing the cardiomyocyte model and hepatocyte model of ischemia-reperfusion, we further prove that after ischemia-reperfusion injury, the cells are in an environment of low polarity, and the microenvironment can be recovered after H₂S treatment.

Significance: An AIE-TICT fluorescence probe capable of cascading responses to H₂S, polarity and viscosity was constructed by using tetraphenylethylene and coumarin moieties. This probe provides a more intuitive and convenient condition for real-time tracking the changes of cellular microenvironment (polarity or viscosity) before and after H₂S treatment of ischemia-reperfusion injury.

Keywords: AIE-TICT probe; Cascade response; Cellular microenvironment; Ischemia-reperfusion injury.