Artemisia-derived carbon dots with excellent pharmacological activities and ROS scavenging for osteoarthritis treatment.

The pharmacological activities of traditional herbal medicine-derived carbon dots (THM-CDs) render them highly promising for applications in biomedicine. However, the interactions between THM-CDs and intracellular proteins have yet to be fully elucidated. Herein, inspired by the traditional vinegar-processing of Artemisia argyi (A. argyi), acetic acid-treated Artemisia argyi-derived carbon dots (AA-CDs) demonstrate excellent resistance to iron death via efficient ROS scavenging and Fe2+ chelating. Notably, multi-omics analysis uncovers a novel whereby AA-CDs directly target and stabilize heat shock protein A5 (HSPA5), thus preventing the degradation of glutathione peroxidase 4 (GPX4), a pivotal negative regulator of ferroptosis. Emerging evidence indicates that ferroptosis plays a critical role in the pathogenesis and progression of osteoarthritis (OA). Consequently, in vitro experiments confirmed that AA-CDs effectively inhibit chondrocyte ferroptosis, consequently mitigating the degradation of the extracellular matrix (ECM). Further in vivo validation in a rat osteoarthritis (OA) model demonstrates that AA-CDs administration remarkably alleviates cartilage erosion, osteophyte formation, and synovitis. Collectively, these findings establish an HSPA5-GPX4 axis-mediated mechanism through which AA-CDs mitigate OA progression, providing novel insights into the bioactivity mechanisms of herbal-derived carbon dots and supporting their development as next-generation ferroptosis inhibitors for OA therapy.