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 (<i>Selenop</i>), cartilage homeostasis (<i>Cytl1</i> and <i>DKK3</i>) and subchondral bone remodeling (<i>Omd</i>). 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.