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.