Logically Activatable Nanoreporter for Multiplexed Time-Phased Imaging Assessment of Hepatic Ischemia-Reperfusion Injury and Systemic Inflammation

Hepatic ischemia-reperfusion injury (HIRI) and induced systemic inflammation is a time-dependent multistage process which poses a risk of causing direct hepatic dysfunction and multiorgan failure. Real-time in situ comprehensive visualization assessment is important and scarce for imaging-guided therapeutic interventions and timely efficacy evaluation. Here, a logically activatable nanoreporter (termed QD@IR783-TK-FITC) is developed for time-phase imaging quantification of HIRI and induced systemic inflammation. The nanoreporters could be used for in vivo ratiometric NIR-IIb fluorescence sensing of reactive oxygen species (ROS), which can depict the in situ hepatic ROS fluctuation for the early diagnosis of HIRI in the initial 3 h. Meanwhile, the ROS-specific reaction releases renal-clearable fluorophore fragments from nanoreporters for monitoring the systematic inflammation induced by HIRI via longitudinal urinalysis. In addition, a functional relationship between digitized signal outputs (NIR-IIb ratios, urinary fluorescence) with hepatic injury scores has been established, realizing precise prediction of HIRI severity and preassessment of therapeutic efficacy. Such a time-phased modular toolbox can dynamically report HIRI-induced systemic inflammation in vivo, providing an efficient approach for HIRI treatment.