Precise Monitoring and Assessing Treatment Response of Sepsis-Induced Acute Lung Hypoxia with a Nitroreductase-Activated Golgi-Targetable Fluorescent Probe

Sepsis-induced acute lung injury (ALI) is mostly attributed to an outbreak of reactive oxygen species (ROS), which makes leukocytes infiltrate into the lung and results in lung hypoxia. Nitroreductase (NTR) is significantly upregulated under hypoxia, which is commonly regarded as a potential biomarker for assessing sepsis-induced acute lung hypoxia. Increasing evidence shows that NTR in the Golgi apparatus could be induced in sepsis-induced ALI. Meanwhile, the prolyl hydroxylase (PHD) inhibitor (dimethyloxalylglycine, DMOG) attenuated sepsis-induced ALI through further increasing the level of Golgi NTR by improving hypoxia inducible factor-1 alpha (HIF-1 alpha) activity, but as yet, no Golgi-targetable probe has been developed for monitoring and assessing treatment response of sepsis-induced ALI. Herein, we report a Golgi-targetable probe, Gol-NTR, for monitoring and assessing treatment response of sepsis-induced ALI through mapping the generation of NTR. The probe displayed high sensitivity with a low detection limit of 54.8 ng/mL and good selectivity to NTR. In addition, due to the excellent characteristics of Golgi-targetable, Gol-NTR was successfully applied in mapping the change of Golgi NTR in cells and zebrafish caused by various stimuli. Most importantly, the production of Golgi NTR in the sepsis-induced ALI and the PHD inhibitor (DMOG) against sepsis-induced ALI were visualized and precisely assessed for the first time with the assistance of Gol-NTR. The results demonstrated the practicability of Gol-NTR for the precise monitoring and assessing of the personalized treatment response of sepsis-induced ALI.