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

Abstract

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.