Recent studies highlight the vital role of oxidative stress and reactive oxygen species (ROS) during progression of osteoarthritis (OA). Attenuating oxidative stress and reducing reactive oxygen species generation in joints represent reasonable strategies for the treatment of osteoarthritis. To address the potential question for clinical translation, and improve the biocompatibility and long-term performance of current antioxidants, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity and first applied to osteoarthritis intervention. Our in vitro results showed that Ta-NH2 NPs were stable with good biocompatibility, and protected viability and hyaline-like phenotype in H2O2-challenged chondrocytes. In addition, the in vivo biodistribution data demonstrated a sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage without organ toxicity and abnormality in hemogram or blood biochemistry indexes. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced osteoarthritis model. This study preliminarily explored the potential of simply modified metal nanoparticles as effective reactive oxygen species scavenging agent for osteoarthritis intervention, and offered a novel strategy to achieve sustained reactive oxygen species suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

Background Osteoarthritis (OA), which involves the dysfunction of articular cartilage, is the most common form of joint disease that results in arthralgia, joint deformation and limited mobility in patients. Recent studies highlighted the vital role of oxidative stress and reactive oxygen species (ROS) during progression of OA. Therefore, attenuating oxidative stress and reducing ROS generation in articular joints represent reasonable strategies for the treatment of OA. However, in addition to instability of current antioxidants caused by fluctuation in osteoarthritic physicochemical microenvironment, poor biocompatibility and short articular joint retention also seriously hindered their clinical application. Results Considering the above-mentioned, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity. Our in vitro results showed that Ta-NH2 NPs had good biocompatibility and stability, and could protect viability and hyaline-like phenotype in chondrocyte under H2O2 challenge. In addition, the in vivo biodistribution data demonstrated sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage with unnoticed organ toxicity and abnormity in hemogram and blood biochemistry analyses. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced OA model. Conclusion This study explored the potential of Ta-NH2 NPs as effective ROS scavenging agent for intra-articular injection, and offered a novel strategy to achieve sustained ROS suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.