Abstract
The ongoing progression of acetaminophen (APAP)-induced liver injury (AILI) resulting from excessive APAP intake can lead to acute liver failure (ALF). This process involves an imbalanced antioxidant system, upregulated inflammatory responses, and excessive accumulation of reactive oxygen and nitrogen species (RONS), which ultimately trigger apoptosis. In the present study, tannic acid-capped tungsten disulfide nanosheets (WS(2)@TA NSs), which are atomic crystals with a 2D structure, a high specific surface area, and abundant phenolic groups, were synthesized using a liquid-phase exfoliation method. WS(2)@TA NSs were investigated as highly effective anti-inflammatory nanomedicines for targeted enrichment therapy of AILI lesions. Enriched WS(2)@TA NSs in the liver were able to scavenge excess RONS, exhibiting potent antioxidant properties. Importantly, in addition of oxidative stress levels reducing, bioactive WS(2)@TA NSs, which are rich in variable valence states, were able to modulate multiple biosignaling pathways including Nrf2-Keap1, NF-κB, and apoptosis in advanced-stage AILI mice model, thereby enhancing liver tolerance to AILI. The present study reveals the clinical potential of WS(2)@TA NSs atomic crystals in targeted enrichment therapy for late-stage AILI lesions.