Abstract

Background Acute lung injury (ALI) is a severe respiratory disease worldwide and is characterized by a high mortality rate. Effective therapeutic interventions remain limited. Although metal-polyphenol coordination polymers (MPCPs) have shown considerable therapeutic potential across diverse pathological conditions, their application in ALI, along with the elucidation of the molecular mechanisms, remains insufficiently explored. Methods Based on the coordination interaction between cerium (Ce) and tannic acid (TA), a Ce-TA nanomaterial was synthesized through a facile and cost-effective method. The properties, stability, radical scavenging activity, and enzyme-like activity of Ce-TA were evaluated. Comprehensive assessments of its therapeutic effects and biosafety were performed using various cell models and a lipopolysaccharide (LPS)-induced ALI mouse model. Results Ce-TA exhibited ultrasmall size and high colloidal stability, efficiently scavenging multiple free radicals via its superoxide dismutase (SOD)-like and catalase (CAT)-like enzyme activities. Ce-TA inhibited H2O2-induced apoptosis and ROS production in BEAS-2B cells and human umbilical vein endothelial cells (HUVECs). Compared with the LPS group, Ce-TA effectively alleviated LPS-induced ALI by ameliorating lung histopathological injury, decreasing lung wet/dry weight (W/D) ratio, myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and reducing inflammatory cytokine levels in vivo via activation of the PI3K/AKT/Nrf2 signaling pathway. Conclusion Ce-TA demonstrated significant anti-inflammatory and antioxidant effects both in vivo and in vitro, with confirmed safety for long-term application. It alleviated LPS-induced ALI by activating the PI3K/AKT/Nrf2 signaling pathway. The facile and economical synthesis of Ce-TA highlights its potential for clinical application, and these advantages make it a promising therapeutic agent for ALI.