High-Fidelity Trapping of Spatial-Temporal Mitochondria with Rational Design of Aggregation-Induced Emission Probes

摘要

High-fidelity trapping of mitochondrial dynamic activity is critical to value cellular functions and forecast disease but lack of spatial-temporal probes. Given that commercial mitochondria probes suffering from low photostability, aggregation-caused quenching effect, and limited signal-to-noise ratio from fluorescence always on in the process of targeting mitochondria, here, the rational design strategy of a novel aggregation-induced emission (AIE) molecular motif and unique insight into the high-fidelity targeting of mitochondria is reported, thereby illustrating the relationship between tailoring molecular aggregation state and mitochondrial targeting ability. This study focuses on how to exactly modulate the hydrophilicity and the aggregated state for realizing "off-on" fluorescence, as well as matching the charge density to go across the cell membrane for mitochondrial targeting. Probe tricyano-methylene-pyridine (TCM-1) exhibits an unprecedented high-fidelity feedback on spatial-temporal mitochondrial information with several advantages such as "off-on" near-infrared characteristic, high targeting capacity, favorable biocompatibility, as well as excellent photostability. TCM-1 also produces reactive oxygen species in situ for image-guided photodynamic anticancer therapy. Through unraveling the relationship between tuning molecular aggregation behavior and organelle-specific targeting ability, for the first time, a unique guide is provided in designing AIE-active probes to explore the hydrophilicity and membrane potential for targeting subcellular organelles.