Real-Time and High-Fidelity Tracking of Lysosomal Dynamics with a Dicyanoisophorone-Based Fluorescent Probe

The development of high-performance probes that can visualize and track the dynamic changes of lysosomes is very important for the in-depth study of lysosomes. Herein, we report that a dicyanoisophorone-based probe (named DCIP) can be used for high-fidelity imaging of lysosomes and lysosomal dynamics. DCIP can be easily prepared and shows strong far-red to near-infrared emissions centered at 653 nm in water with a huge Stokes shift (224 nm), high quantum yield (Φ = 0.15), high pKa value (∼8.79), and good biocompatibility. DCIP also shows good cell permeability and can label lysosomes rapidly with bright fluorescence without a time-consuming washing process before imaging. DCIP also possesses good photostability and negligible background, making it effective for long-term and high spatiotemporal resolution (0.44 s of exposure) imaging of lysosomes. Moreover, DCIP achieved high-fidelity tracking of lysosomal dynamics at an extremely low concentration (1 nM). Finally, we also demonstrated that DCIP could real-time track the interactions of lysosomes with other organelles (damaged mitochondria as a model) and image the drug-escape processes from lysosomes. All of the results show that DCIP holds broad prospects in lysosome-related research.