Polyphenol-regulated Cu-based broad-spectrum anti-oxidants to overcome oxidative stress

Copper-based nanozymes have emerged as promising therapeutic agents for oxidative stress-related diseases due to their enzyme-mimicking properties. However, their development is still limited by poor biocompatibility, insufficient broad-spectrum free radical scavenging ability, and potential toxicity from Cu 2+ leakage. To address these challenges, we developed Cu@EA-BTC, a broad-spectrum antioxidant material, by integrating ellagic acid (EA) into copper-based metal-organic frameworks (Cu@BTC). The Cu@BTC serves as a stable copper source, while the EA endows the Cu@EA-BTC with broad-spectrum ROS scavenging and enhanced catalase (CAT)-like activity via facilitating the reduction of Cu 2+ to Cu + . As a result, the Cu@EA-BTC exhibits superior antioxidant properties and excellent biocompatibility, including both cellular and blood compatibility. Meanwhile, the Cu@EA-BTC effectively protects immune cells from oxidative damage, which indicates its potential for oxidative stress-related therapies. This study provides a promising strategy for developing safe and efficient nanozyme-based antioxidant materials for biomedical applications.