Redox-immune modulating gadolinium vanadate based nanozymes for osteoarthritis therapy

Osteoarthritis (OA) remains a highly prevalent degenerative joint disorder driven by a self-reinforcing cycle of reactive oxygen species (ROS) accumulation, inflammatory amplification, and chondrocyte dysfunction within the joint microenvironment. Herein, we developed a rare-earth (RE) doped-engineered gadolinium vanadate-based bioactive nanosystem through rational lanthanide modulation and pterostilbene loading for synergistic regulation of OA progression. Through precisely controlled RE lattice doping and electronic-structure optimization, GVCP exhibits potent enzyme-mimetic ROS-scavenging activity, thereby alleviating oxidative stress and suppressing inflammation in the pathological joint microenvironment. Beyond this upstream microenvironmental regulation, GVCP directly preserves chondrocyte homeostasis by attenuating apoptosis, accompanied by modulation of the p53 signaling pathway and restoration of the Bax/BCL-2 balance. Meanwhile, GVCP promotes macrophage polarization toward the reparative M2 phenotype, thereby contributing to immune remodeling favorable for cartilage protection. In addition, DFT calculations further reveal Re-doped-induced electron-transfer characteristics and catalytic energetics underlying the enhanced redox activity of the nanosystem. In vivo results further demonstrated that GVCP markedly mitigates cartilage degeneration, leading to effective attenuation of OA progression with good biocompatibility. As a result, this work proposes a bioactive nanotherapeutic strategy that combines upstream microenvironment regulation with downstream pathway intervention, offering a comprehensive antioxidant-immune modulation nanoplatform.