Multifunctional Nanozyme PDA-Cr2O3 for the Treatment of Osteoarthritis

Can Li,1,* Guiju Chen,1,* Xiongwei Yan,2,* Bingyang Hu,3,* Xiangyun Zhang,4 Jun Song2,5 1Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 2Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 3Department of Emergency Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 4Central Sterilization Supply Department, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China; 5Hospital Administration Office, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Song; Email [email protected] Xiangyun Zhang, Email [email protected]: 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. Keywords: osteoarthritis, reactive oxygen species, polydopamine, chromium sesquioxide, nanozyme