Epigallocatechin-3-gallate (EGCG) based metal-polyphenol nanoformulations alleviates chondrocytes inflammation by modulating synovial macrophages polarization

The activation of M1-type macrophages are dominant cells secreting proinflammatory present within the inflamed synovium in the progression of osteoarthritis (OA). Increased oxidative stress, such as redundant ROS and hydrogen peroxide (H₂O₂), are important factors in driving macrophages to polarize into M1 type. In this study, metal-polyphenol nanoformulations (Cu-Epigallocatechin-3-gallate (Cu-EGCG) nanosheets) were synthesized through the coordination interaction between EGCG and copper ions, which possessed the antioxidant effect of EGCG and anti-inflammatory of Cu²⁺. Results showed that Cu-EGCG nanosheets were biocompatible and the Cu²⁺ could be sustained released from the nanoparticles. Cu-EGCG nanosheets with multienzyme-like antioxidative activity could effectively scavenge the excessive intracellular ROS, leading to significantly decreased expression of the pro-inflammatory cytokines, which could reduce the expression of M1-type macrophages and exhibit excellent promotion on shifting macrophages to M2 phenotypes. Moreover, the secreted factor from the cell supernatant of Cu-EGCG treated macrophages exhibited anti-inflammatory potential in chondrocytes of inflamed synovial joints. This study suggests a novel strategy for OA therapy by using metal-polyphenol nanoformulations targeting macrophages.