Engineering of Reversible NIR‐II Redox‐Responsive Fluorescent Probes for Imaging of Inflammation In Vivo

The second near‐infrared (NIR‐II) fluorescent imaging shows great potential for deep tissue analysis at high resolution in living body owing to low background autofluorescence and photon scattering. However, reversible monitoring of redox homeostasis using NIR‐II fluorescent imaging remains a challenge due to the lack of appropriate probes. In this study, a series of stable and multifunctional NIR‐II dyes (NIR‐II Cy3s) were constructed based on trimethine skeleton. Significantly, introducing the 1,4‐diethyl‐decahydroquinoxaline group to the NIR‐II Cy3s not only effectively increased the wavelength, but also served as an effective response site for HClO, which can be restored by reactive sulfur species (RSS). Based on this, NIR‐II Cy3s were used for reversible monitoring of HClO/RSS‐mediated redox processes in the pathophysiology environment. Finally, NIR‐II Cy3‐988 was successfully utilized for assessment of the redox environments and drug treatment effects in acute inflammation model. We report a new class of trimethine skeleton NIR‐II fluorophores (NIR‐II Cy3s) with improved stability over traditional heptamethine NIR‐II fluorophores and emission above 1000 nm. The NIR‐II Cy3s can reversibly respond to HClO and reactive sulfur species (RSS) and can serve as an effective platform for the reversible monitoring of the HClO/RSS‐mediated redox process in a pathophysiology environment. Finally, we applied NIR‐II Cy3‐988 to the reversible assessment of the redox environment and dynamic effect of drug treatment in an acute inflammation model and of redox potential changes during liver injury and repair.