Multifunctional Nanozyme PDA-Cr2O3 for the Treatment of Osteoarthritis.

Abstract

Introduction: Osteoarthritis (OA) is one of the major menaces to human health. Currently, no sufficiently effective medications are available to treat OA clinically. OA is an inflammatory joint disorder. The overproduction of reactive oxygen species (ROS) plays a critical role in initiating and developing OA pathogenesis. ROS scavenging has become a vital target for OA therapy. Although chromium sesquioxide (Cr₂O₃) nanoparticle has been proven to have excellent ROS scavenging ability, its clinical application is limited due to its poor biocompatibility. Polydopamine (PDA) is an excellent carrier with outstanding biocompatibility. PDA-based nanomaterials exhibit significant potential for various ROS-related diseases.

Methods: PDA was synthesized through oxidative autopolymerization of dopamine in an alkaline environment. Subsequently, the novel nanozyme PDA-Cr₂O₃ was synthesized by loading Cr₂O₃ onto PDA nanoparticles with the assistance of hydrazine hydrate. Afterward, the cytotoxicity and ROS scavenging capacity of PDA-Cr₂O₃ were examined. Finally, the ability of PDA-Cr₂O₃ to treat OA was explored at both cellular and animal levels.

Results: PDA-Cr₂O₃ had low cytotoxicity and toxic side effects in vivo. Moreover, PDA-Cr₂O₃ exhibited a remarkable capacity to scavenge ROS both in cell-free in vitro systems, such as kit-based assays, and in cellular models. It also dramatically decreased the transcriptional level of inflammation-associated genes and the secretion of inflammatory factors of the OA chondrocytes. In animal experiments, PDA-Cr₂O₃ markedly suppressed the progression of OA.

Conclusion: PDA-Cr₂O₃ nanozyme had good biocompatibility and could effectively suppress the development of OA by efficiently scavenging ROS, which has important application prospects in OA treatment. This study might offer some new ideas for the treatment of ROS-related diseases.