Polysiloxane-based ratiometric fluorescent probe for monitoring lysosomal autophagy pathway in three distinguishable channels

Abstract

Autophagy is an essential process for the degradation of malfunctional organelles and the response to cancer immunotherapy. The occurrence of defective autophagy is correlated to obesity, aging, neurological diseases, inflammation and tumors. Therefore, it is urgent to accurately depict the autophagic process. We herein architecture a polysiloxane-based probe (PA-1) that was lysosome targeted and pH-responsive for discerning autophagy process. We have demonstrated that PA-1 enabled specific visualization of lysosomal autophagy. PA-1 also detected the down-regulation of the pH value that accompanied the autophagy process under starvation stimulation. During autophagy, the green fluorescence of some spots in the lysosomes gradually decreased along with the emergence of strong agglomerated red fluorescence, which might be caused by the membrane fusion of lysosomes and autophagosomes. The location of the autolysosome could be precisely displayed by the ratio image. In addition, we observed that the autophagy inhibitor CQ could increase the pH of the intracellular environment and inhibit autophagy. The design strategy will broaden the research field of polysiloxane in cellular physiological processes and serves as a candidate for basic research on autophagic processes and effective therapeutic strategies for autophagy-related diseases.