Spotlight on Mitochondrial Health: A Trailblazing Fluorescent Tool for Cancer Detection and Surgical Guidance

Mitochondria play a pivotal role in maintaining normal physiological functions. Mitochondrial autophagy, namely, mitophagy, is a selective catabolic disposal of impaired mitochondria through an autophagic mechanism during episodes of mitochondrial harm. This selective removal, e.g., mitophagy, is essential for mitochondrial quality control and is closely related to the pathogenesis of many diseases. The abnormal buildup of defective mitochondria in vivo was used as a target to prevent the development of cancer. The mitochondrial autophagy process of disease-related cells is usually accompanied by a decrease in polarity and pH, and the fluorescence sensing effects caused by these two factors are usually contradictory. Here, we propose a reinventing strategy to develop a dual-channel and dual-responsive fluorescent probe HDTVB that is capable of tracking mitochondrial autophagy by monitoring fluctuations in mitochondrial pH and polarity. Based on the aggregation-induced emission (AIE) moiety and hemicarpine moiety push-pull system with activated near-infrared (NIR) emission and pH-activatable cyclization reaction, HDTVB was able to differentiate tumors from normal sites via polarity- and acidity-triggered structural changes of the probe in the course of mitochondrial autophagy. HDTVB is expected to be applied to clinical diagnosis and tumor excision guided by fluorescence, offering a new route in physiological and biochemical research.