Self-Assembled EGCG Nanoparticles Achieved Long-Term ROS Scavenging to Delay Osteoarthritis Progression

Oxidative stress disrupts the synthesis–degradation balance of the extracellular matrix in osteoarthritic (OA) cartilage, resulting in the loss of type II collagen (COLII). Here, we developed self-assembled nanoparticles (PE@NPs) driven by hydrophobic interaction, π–π stacking interactions and hydrogen bonding, forming an epigallocatechin-3-gallate (EGCG) core and a polyethylene glycol (PEG) shell. Compared with free EGCG, which possesses potent but short-lived antioxidant activity, PE@NPs improved molecular stability, extending reactive oxygen species scavenging activity to 24 h. Furthermore, PE@NPs significantly suppressed interleukin-1 β-induced COLII degradation in OA chondrocytes. Transcriptomic analysis revealed that PE@NPs upregulated genes involved in antioxidant defense ( Selenop ), cartilage homeostasis ( Cytl1 and DKK3 ) and subchondral bone remodeling ( Omd ). In vivo, PE@NPs exhibited a more significant therapeutic effect than free EGCG, notably attenuating COLII degradation and improving subchondral bone mass, thereby delaying OA progression. Overall, these findings identify PE@NPs as a safe and effective therapeutic approach for OA.