Logically Activatable\nNanoreporter for Multiplexed\nTime-Phased Imaging Assessment of Hepatic Ischemia-Reperfusion Injury\nand Systemic Inflammation

Hepatic ischemia-reperfusion injury (HIRI) and induced\nsystemic\ninflammation is a time-dependent multistage process which poses a\nrisk of causing direct hepatic dysfunction and multiorgan failure.\nReal-time in situ comprehensive visualization assessment is important\nand scarce for imaging-guided therapeutic interventions and timely\nefficacy evaluation. Here, a logically activatable nanoreporter (termed\nQD@IR783-TK-FITC) is developed for time-phase imaging quantification\nof HIRI and induced systemic inflammation. The nanoreporters could\nbe used for in vivo ratiometric NIR-IIb fluorescence sensing of reactive\noxygen species (ROS), which can depict the in situ hepatic ROS fluctuation\nfor the early diagnosis of HIRI in the initial 3 h. Meanwhile, the\nROS-specific reaction releases renal-clearable fluorophore fragments\nfrom nanoreporters for monitoring the systematic inflammation induced\nby HIRI via longitudinal urinalysis. In addition, a functional relationship\nbetween digitized signal outputs (NIR-IIb ratios, urinary fluorescence)\nwith hepatic injury scores has been established, realizing precise\nprediction of HIRI severity and preassessment of therapeutic efficacy.\nSuch a time-phased modular toolbox can dynamically report HIRI-induced\nsystemic inflammation in vivo, providing an efficient approach for\nHIRI treatment.