Leveraging Activatable Janus Nanoprobes for NIR‐II Imaging and Enzyme‐Like Activity in Monitoring Liver Fibrosis

Abstract Liver fibrosis presents a significant global health challenge due to its potential progression to cirrhosis, liver failure, or hepatocellular carcinoma, highlighting the necessity for precise imaging of fibrosis progression. Here, a straightforward synthesis method is proposed to design bioresponsive nanoprobes capable of achieving high‐resolution bioimaging of liver fibrosis. Janus MnO 2 ‐coated Ag/Ag 2 S nanoparticles modified by polyethylene glycol (denoted as jMAP) can inherit both the activatable properties from Ag/Ag 2 S and MnO 2 components in the pathological microenvironment. Multiple lines of evidence supported that overexpressed levels of reactive oxygen species (ROS) in liver fibrosis efficiently transformed jMAP nanoprobes to Ag 2 S products, activating bright fluorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm). In addition, the catalase‐like and superoxide dismutase‐like activities of jMAP probes reduce hypoxia and oxidative stress with a clearance rate of about 73.3% toward ROS, thereby downregulating hypoxia‐inducible factor (HIF‐1 α ) and NADPH oxidase‐4 (NOX‐4) by 49.5% and 47.9%, respectively. Overall, the developed jMAP probes demonstrate impressive diagnostic accuracy, offering transformative prospects for liver fibrosis diagnosis.