Selenium nanoparticles alleviate cobalt toxicity in artificial joint metal prostheses by inhibiting ferroptosis through activation of the PRDX6/GPX4 pathway.

The long-term implantation of metallic joint prostheses results in the release of cobalt nanoparticles (CoNPs), leading to local and even systemic toxic reactions that pose risks to patient health. Previous studies have suggested that CoNPs-induced cytotoxicity may be associated with excessive oxidative stress and ferroptosis. Selenium nanoparticles (SeNPs), known for their anti-ferroptotic properties, have potential as surface coatings for metal implants. This study aims to investigate the role and mechanisms of SeNPs in inhibiting ferroptosis and mitigating cobalt-induced toxicity, thereby offering a mechanistic rationale for improving the material properties of metal prostheses. We first conducted molecular analyses on tissue samples from patients undergoing hip joint revision surgery, which revealed activation of ferroptosis-related signaling pathways. We then synthesized SeNPs capable of effective internalization by bone marrow-derived stromal cells (BMSCs). In vitro, 400 μM CoNPs induced hallmark features of ferroptosis in BMSCs by suppressing the SLC7A11/GPX4 axis and activating the HIF-1α/HO-1 signaling pathway. In contrast, treatment with 40 μM SeNPs upregulated PRDX6 and GPX4, thereby attenuating ferroptosis and preserving cell viability. Finally, intra-articular injection of SeNPs into mouse knee joints significantly alleviated CoNPs-induced local toxic responses, including synovial hyperplasia and cartilage destruction. Overall, this study provides novel insights into the ferroptosis-dependent mechanisms underlying CoNPs-induced toxicity and highlights the therapeutic potential of SeNPs as a detoxifying agent. These findings offer a mechanistic foundation for targeted detoxification strategies and inform the development of improved metal prosthetic materials.