LAUSR

Liver fibrosis is a major stage in the development of liver diseases and it is important to investigate its pathogenesis for early intervene or even reversing. Recent studies have found that intestinal disease can aggravate liver fibrosis through the role of the "gut-liver axis". Hypoxia is considered to be a typical characteristic of many diseases including ulcerative colitis and liver fibrosis. However, there is no fluorescent probe for hypoxia detection to investigate "gut-liver axis". Herein, we design and synthesize a turn-on fluorescent probe termed Cy-AP, which displays high sensitivity and selectivity to hypoxia given by sodium dithionite (Na2S2O4) in vitro with near-infrared (NIR) emission (735 nm). And the possible response mechanism of Cy-AP towards hypoxia is given and proved by HPLC, MS and theory calculation. Moreover, on the basis of low cell cytotoxicity, the probe is successfully applied in visualizing hypoxia in four cell lines (HepG2, HCT116, HeLa and MCF-7 cells) by fluorescence imaging, flow cytometry and 3D imaging. Furthermore, due to its NIR emission, Cy-AP can monitor the hypoxia condition in vivo such as liver fibrosis mice and ulcerative colitis mice model. In particular, the probe can validate the existence and mechanism of "gut-liver axis" in vivo by monitoring hypoxia. To the best of our knowledge, this is the first report to describe a strategy for study "gut-liver axis" by a NIR hypoxia-sensitive fluorescent probe, which will provide some powerful support for delaying the progression of liver fibrosis and thus promoting the treatment of liver disease.