Selective Twin NIR‐IIb Ratiometric Luminescence Nanoprobes Enable the Accurate Visualization of MPO‐Mediated Oxidative Stress in Acute Liver Injury

Abstract Oxidative stress, orchestrated by myeloperoxidase (MPO), plays crucial roles in the progression of many diseases. Nonetheless, the role of MPO‐mediated oxidative stress in distinct factor‐induced acute liver injuries (ALI) is still up for dispute, mainly due to the lack of probes for in vivo monitoring of MPO releases. Here, a highly selective MPO probe (CSQ) based on the epoxidation biochemical reaction within the MPO‐H₂O₂‐Cl⁻ system is screened to construct dual near infrared‐IIb (NIR‐IIb) ratiometric (F_{1550Em, 808Ex}/F_{1550Em, 980Ex}) luminescence nanoprobes by integrating CSQ onto down conversion nanoparticles (DCNPs) with and without liver‐targeting moiety (twin NIR‐IIb nanoprobes). Liver‐targeting probes are employed to monitor MPO release, whereas non‐liver‐targeting probes are utilized to assess MPO activity across all cell types. Using twin NIR‐IIb nanoprobes, the MPO‐mediated oxidative stress progressively increased are observed in carbon tetrachloride (CCl₄)‐induced ALI over 12 h. In contrast, the MPO‐mediated oxidative stress in acetaminophen (APAP)‐induced ALI initially increased, peaked within 3 h, and then rapidly weakened to normal levels within 12 h. Importantly, the differential release of MPO from neutrophils/Kupfer cells to extracellular fluids in the two types of ALI is revealed. This work reveals significant differences in MPO distribution and the role of MPO‐mediated oxidative stress in CCl₄ and APAP‐induced ALI.