Sustained intra-articular reactive oxygen species scavenging and alleviation of osteoarthritis by biocompatible amino-modified tantalum nanoparticles

Abstract

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.

Keywords: ROS scavenging agent; catalase activity; osteoarthritis; oxidative stress; tantalum nanoparticles.