A Novel Curcumin‐Loaded Nanoplatform Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis

Abstract Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin‐loaded nanoparticles (Cur‐NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe 2 ⁺), and Acyl‐CoA Synthetase Long‐Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron‐chelating properties. The in vitro anti‐ferroptotic effects of Cur‐NPs are thoroughly investigated. The findings indicate that Cur‐NPs decrease the expression of ferroptosis markers such as ROS, Fe 2 ⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur‐NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur‐NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur‐NPs exhibit enhanced chondroprotective effects through anti‐ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.