Dual-Response and Dual-Targeting Probe Based on the Quinolinothiazole Salt Capable of Decoding Cellular Stress and Cellular State

The functional state of subcellular organelles served as a fundamental indicator of the cellular health. However, conventional fluorescent probes were largely limited to single-parameter detection, failing to capture coordinated interorganellar dynamics during pathological processes. Here, we developed a novel fluorescent probe, QTNP, based on a quinolinethiazolium scaffold. QTNP featured a large Stokes shift (∼179 nm in Toluene) and dual-response capability, allowing simultaneous sensing of the local pH and nucleic acid activity. The limit of detections (LOD) toward DNA and RNA were calculated to be 1.43 μg/mL and 0.89 μg/mL, respectively, indicating the high sensitivity of QTNP. Furthermore, QTNP achieved dual targeting of mitochondria and nucleoli. Cell imaging displayed QTNP dynamically decoded cellular stress responses: it exhibited a 1.8-fold fluorescence enhancement in CCCP-induced mitochondrial dysfunction and showed significant, reversible quenching (6.0-fold decrease in total intensity) during ferroptosis, which was fully reversible upon the addition of Fer-1. Notably, based on its sensitive response to nucleic acid activity across different physiological states, QTNP reliably distinguished normal, cancerous, and senescent cells via baseline fluorescence intensity, showing 15 to 20-fold stronger signals in cancerous cells compared to normal cells. Therefore, this work provides a versatile tool for studying organelle interactions and cellular states in living systems.