Simultaneous detection of H₂S and viscosity in pancreatic cancer with a lysosome-targeted NIR fluorescent probe.

Pancreatic cancer is one of the most aggressive malignancies and has one of the lowest survival rates among all major cancers. Accurate diagnosis at an early stage can improve patient survival. Near-infrared fluorescent (NIRF) probes have been emerged as promising tools for tumor imaging due to their superior optical properties. However, most probes suffer from significant limitations in the simultaneous detection of multiple tumor biomarkers, which may lead to false-positive signals. Herein, we constructed a novel lysosome-targeted NIRF probe (LNX-HS) incorporating an azide moiety and an ethylene bridge, for the detection of HS and viscosity. The H₂S-triggered reduction of the azide group led to the release of LNX-OH, initiating intramolecular charge transfer (ICT), followed by a viscosity-mediated restriction of molecular rotation that suppressed the twisted ICT (TICT) process. As a result, the probe exhibited a significant fluorescence enhancement at 700 nm. Biological validation demonstrated the probe could differentiate pancreatic cancer cells from normal cells by visualizing the elevated levels of both biomarkers. Moreover, this probe was successfully applied in a murine pancreatic cancer model, providing a powerful tool for the early diagnosis of pancreatic cancer.