Ratiometric photoacoustic imaging of endoplasmic reticulum polarity in injured liver tissues of diabetic mice

As one of the complications of diabetes, liver injury results in significant hazards. Therefore, accurately diagnosing diabetes-induced liver injury beforehand is crucial for the warning and treatment of hepatic diseases. Diabetes-induced liver injury can cause changes in the microstructure and morphology of liver tissue, leading to changes in the hydrophilic and hydrophobic domains in the endoplasmic reticulum (ER), which is closely associated with changes in cellular ER polarity. So, differences in the ER polarity can indicate the degree of diabetes-induced liver injury. Herein, we develop a new fluorescent and photoacoustic dual-mode probe, ER-P, for detection of the ER polarity of liver tissue in normal and diabetic mice. Upon excitation with a 633 nm laser, ER-P showed increasing fluorescence intensity at 800 nm accompanying a decline in the polarity. Due to its polarity-sensitivity, ER-P was utilized for confocal fluorescence imaging in live cells, and the results demonstrate that ER-P can exclusively accumulate in the ER and indicate an increase in the polarity during ER stress. Importantly, ER-P displayed different absorbance intensities at 700 nm and 800 nm in different polarity environments because of intramolecular charge transfer. The photoacoustic intensity ratios between 700 nm and 800 nm will enable quantification of polarity to be achieved. The ratiometric photoacoustic imaging data demonstrate that the polarity of the liver tissue of diabetic mice is higher than that of the liver tissue of normal mice. Meanwhile, after treatment with the antidiabetic drug metformin, diabetic mice exhibit a reduced polarity environment in their liver tissue. The proposed study may serve as a new approach for the early diagnosis and therapeutic evaluation of diabetes-induced liver injury.