Liver-Targeted Near-Infrared Fluorescence/Photoacoustic Dual-Modal Probe for Real-Time Imaging of <i>In Situ</i> Hepatic Inflammation

Abstract

Early diagnosis of hepatic inflammation is the key to timely treatment and avoid the worsening of liver inflammation. Near-infrared fluorescence (NIRF) probes have high sensitivity but low spatial resolution in lesion imaging, while photoacoustic (PA) imaging has good spatial location information. Therefore, the development of a NIRF/PA dual-modal probe integrated with high sensitivity and spatial location feedback can achieve an accurate early diagnosis of hepatic inflammation. Here, we report an activatable NIRF/PA dual-modal probe (<b>hCy-Tf-CA</b>) for the detection of the superoxide anion (O₂^·-) in early hepatic inflammation. <b>hCy-Tf-CA</b> showed high selectivity and sensitivity for detecting O₂^·- fluctuation <i>in vitro</i>. More importantly, by introducing hepatocyte-targeting cholic acid (<b>CA</b>), the probe successfully achieved accurate <i>in situ</i> imaging of acute inflammatory liver injury (AILI) and autoimmune hepatitis (AIH) <i>in vivo</i>. The introduced <b>CA</b> not only promotes the hepatic targeting accumulation of probes but also improves the performance of low background dual-modal imaging <i>in vivo</i>. Therefore, <b>hCy-Tf-CA</b> provides an effective strategy for significantly improving <i>in situ</i> imaging performance and holds great potential for early, sensitive, and accurate diagnosis of hepatic inflammation.