Application of Cerium-Tannic Acid-Formaldehyde Coordination Polymer Colloidal Nanomaterials to Alleviate Lipopolysaccharide-Induced Acute Lung Injury

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 H 2 O 2 -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.