Activatable Near‐Infrared IIb Rare‐Earth Nanoprobe for Early Monitoring Chemotherapy‐Induced Liver Injury

Abstract Clinical chemotherapy drugs may induce severe hepatic damage and toxicity with prolonged use, which is a major concern among the various adverse effects associated with chemotherapy. Early diagnosis of chemotherapy‐induced liver injury (CILI) is critical to prevent its progression into other liver diseases and potential liver failure. However, there is currently a lack of effective tools for early monitoring of CILI. To address this issue, it is developed a glutathione (GSH)‐activated ratiometric second near‐infrared (NIR‐II) nano‐probe, HCy‐CL‐RENPs, which utilizes rare earth ions‐doped nanoparticles (RENPs) as the luminescence signal reporters and hemicyanine dye HCy‐CL as the recognition unit to react with GSH, thereby modulating the NIR‐IIb emission of RENPs. This probe exhibits high sensitivity and specificity for detecting GSH, along with excellent biocompatibility. Utilizing HCy‐CL‐RENPs, it is accurately evaluated the hepatotoxicity of different chemotherapy drugs and successfully detected CILI within 5 h after drug administration, significantly earlier than existing methods such as serum enzyme detection and biopsy. These findings indicate that the probe can facilitate early assessment of liver injury by monitoring changes in GSH levels, providing a robust tool for the early diagnosis of CILI and guiding personalized treatment strategies.