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 MnO₂-coated Ag/Ag₂S nanoparticles modified by polyethylene glycol (denoted as jMAP) can inherit both the activatable properties from Ag/Ag₂S and MnO₂ 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 Ag₂S 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-1α) 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.