Reactive oxygen species-sensitive fenofibrate-loaded dextran nanoparticles in alleviation of osteoarthritis

Osteoarthritis (OA) stands as a prevalent chronic joint pathology, emerging as a leading cause of disability on a global scale. However, the current therapeutic efficacy in OA treatment remains unsatisfactory. Chondrocyte Ferroptosis has become to a critical target for OA treatment, while the fabrication of nanomedicines emerges as a promising strategy for OA treatment. Nevertheless, there exists a paucity of reported nanomedicine systems designed to combat chondrocyte Ferroptosis for OA alleviation. In light of this, our study introduced a Reactive Oxygen Species (ROS)-sensitive fenofibrate-loaded targeted nanoparticle (FN-CNPs) as a means of alleviating OA by suppressing chondrocyte Ferroptosis. In vitro investigations demonstrated the FN-CNPs can achieve this through the reduction of lipid peroxidation and ROS levels, as well as the elevation of anti-ferroptosis markers (GPX4, FSP1, and ACSL3). Consequently, FN-CNPs exhibited significant anti-inflammatory effects and downregulated the expression of key catabolic mediators in vitro. Furthermore, in vivo studies underscored the ability of FN-CNPs to alleviate OA progression and protect cartilage. Collectively, these findings highlight the efficacy of FN-CNPs in mitigating OA progression by suppressing chondrocyte Ferroptosis via regulating ROS levels, antioxidant systems and lipid metabolism of chondrocytes.