NIRII‐HDs: A Versatile Platform for Developing Activatable NIR‐II Fluorogenic Probes for Reliable In Vivo Analyte Sensing

Small-molecule-based second near-infrared (NIR-II) activatable fluorescent probes can potentially provide a high target-to-background ratio and deep tissue penetration. However, most of the reported NIR-II activatable small-molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII-HDs, a novel dye scaffold optimized for NIR-II probe development. In particular, dye NIRII-HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR-II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII-HD5 dye, we designed three target-activatable NIR-II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR-II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity.