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.