Development of near-infrared lysosomal pH-activatable fluorescent probe for real-time visualization of autophagy progression

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Vol. 464; p. 142554
• Main Authors: Feng, Bin, Ma, Yeshuo, Zheng, Fan, Huang, Xueyan, Feng, Xueping, Zhang, Kexiang, Liu, Li, Chen, Fei, Zeng, Wenbin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.05.2023
• Subjects: Acetaminophen-induced liver injury; Autophagy; Hemicyanine; Lysosome-targeting; Near-infrared; Acetaminophen-induced liver injury; Hemicyanine; Autophagy; Near-infrared; Lysosome-targeting
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2023.142554

[Display omitted] •A novel lysosome-targeted probe (Lyso-QL) with pH-activatable NIR fluorescence was developed with high sensitivity and selectivity.•Lyso-QL presents a fast, reversible, and steady response to pH change and remarkerble Stokes shift.•Lyso-QL was successfully applied for motoring the autophagy progression under nutrient-deprivation conditions and pharmacological modulation.•The abnormal autophagic level during drug-induced liver injury was demonstrated with novel probe.•High sensitiveness was achieved with NIR signals up to 150 μm in the tomography experiment. As the central role in maintaining physiological homeostasis, tracking the autophagy in living cells is highly desired in biological research and pharmacologic development. Herein, a lysosome-targeted pH-activatable probe (Lyso-QL) with emission at near-infrared region (NIR) was developed for monitoring the progression of autophagy. During autophagy progress, the double-membraned autophagosomes are engulfed into lysosomes to provide autolysosomes, exhibiting significantly enhanced acidification. Based on the characteristic, the real-time monitoring of autophagic flux were realized by evaluating the pH changes in these acidic compartments with Lyso-QL under nutrient-deprivation conditions as well as pharmacological induction. Importantly, through the NIR changes, the modulation of tamoxifen on autophagic levels in estrogen receptor-negative cancer cells was disclosed. Further, the elevated hepatic autophagy in mice during acetaminophen-induced liver injury was revealed, and the N-acetylcysteine pretreatment was demonstrated with a certain protective effect to restore the autophagic levels. The study demonstrates probe Lyso-QL would provide an edge for mechanistic insights into autophagy and evaluating the activities of autophagy modulators.