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논문 기본 정보

자료유형
학술저널
저자정보
Fan Zheng (Xiangya School of Pharmaceutical Sciences Central South University) Yeshuo Ma (The Third Xiangya Hospital Central South University) Jipeng Ding (Xiangya School of Pharmaceutical Sciences Central South University) Shuai Huang (Xiangya School of Pharmaceutical Sciences Central South University) Shengwang Zhang (The Third Xiangya Hospital Central South University) Xueyan Huang (Xiangya School of Pharmaceutical Sciences Central South University) Bin Feng (Xiangya School of Pharmaceutical Sciences Central South University) Hongliang Zeng (Research Institute of Chinese Medicine Hunan Academy of Chinese Medicine) Fei Chen (Xiangya School of Pharmaceutical Sciences Central South University) Wenbin Zeng (Xiangya School of Pharmaceutical Sciences Central South University)
저널정보
한국생체재료학회 생체재료학회지 생체재료학회지 제27권
발행연도
2023.3
수록면
1,674 - 1,685 (12page)
DOI
https://doi.org/10.1186/s40824-023-00409-3

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Background Autophagy is a critical self-eating pathway involved in numerous physiological and pathological pro cesses. Lysosomal degradation of dysfunctional organelles and invading microorganisms is central to the autophagy mechanism and essential for combating disease-related conditions. Therefore, monitoring fuctuations in the lyso somal microenvironment is vital for tracking the dynamic process of autophagy. Although much efort has been put into designing probes for measuring lysosomal viscosity or pH separately, there is a need to validate the concurrent imaging of the two elements to enhance the understanding of the dynamic progression of autophagy. Methods Probe HFI was synthesized in three steps and was developed to visualize changes in viscosity and pH within lysosomes for real-time autophagy tracking. Then, the spectrometric determination was carried out. Next, the probe was applied to image autophagy in cells under nutrient-deprivation or external stress. Additionally, the per formance of HFI to monitor autophagy was employed to evaluate acetaminophen-induced liver injury. Results We constructed a ratiometric dual-responsive probe, HFI, with a large Stokes shift over 200 nm, dual wavelength emission, and small background interference. The ratiometric fuorescent signal (R=I 610/I 460) of HFI had an excellent correlation with both viscosity and pH. More importantly, high viscosity and low pH had a synergistic promotion efect on the emission intensity of HFI, which enabled it to specially lit lysosomes without disturbing the inherent microenvironment. We then successfully used HFI to monitor intracellular autophagy induced by starva tion or drugs in real-time. Interestingly, HFI also enabled us to visualize the occurrence of autophagy in the liver tissue of a DILI model, as well as the reversible efect of hepatoprotective drugs on this event. Conclusions In this study, we developed the frst ratiometric dual-responsive fuorescent probe, HFI, for real-time revealing autophagic details. It could image lysosomes with minimal perturbation to their inherent pH, allowing us to track changes in lysosomal viscosity and pH in living cells. Ultimately, HFI has great potential to serve as a useful indicator for autophagic changes in viscosity and pH in complex biological samples and can also be used to assess drug safety.
#Autophagy visualization #Fluorescent probe #Lysosome-specifc #Ratiometric imaging #Dual-responsive #pH #Viscosity #Acetaminophen-induced liver injury

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