HPB@LA@PDA nanoplatform ameliorates osteoarthritis by scavenging reactive oxygen species and remodelling the inflammatory microenvironment: An in vitro and in vivo study

Osteoarthritis (OA) is an irreversible degenerative disease of articular cartilage that commonly occurs in the middle-aged and elderly people. However, effective intervention for early and middle-stage OA is still limited due to its complex and multifactorial nature. Excessive reactive oxygen species (ROS) and the inflammatory microenvironment are considered to play crucial roles in the occurrence and development of OA. Here, a novel HPB@LA@PDA nanoplatform is designed, which utilizes the mimicking enzyme activity of hollow prussian blue (HPB) nanozymes and antioxidant activity of lipoic acid (LA), to synergistically scavenge ROS and remodel the OA microenvironment. HPB@LA@PDA was firstly synthesized and the characterizations were confirmed by TEM, DLS, XPS, FTIR, UV–Vis, and XRD methods. It exhibited excellent multienzyme-like (SOD, GPx, CAT and POD-like) activities and antioxidant activities, converting •O 2 − , H 2 O 2 , •OH and reactive nitrogen species into harmless products. Importantly, at both the cellular and animal levels, we found HPB@LA@PDA could effectively scavenge excess ROS, protect against ROS-induced oxidative stress, apoptosis and ferroptosis, and ameliorate mitochondrial dysfunction, reduce inflammatory expression, and inhibit macrophage polarization in the chondrocytes. Finally, the results of in vivo study demonstrated that HPB@LA@PDA exhibited good biocompatibility and excellent therapeutic efficacy in the OA rat model. Micro-CT scaning, histopathological and immunofluorescence staining and western blotting analysis confirmed that HPB@LA@PDA attenuated the progression of OA by way of scavenging reactive oxygen species and remodelling the inflammatory microenvironment. The combination of drug and nanoenzyme vehicle offers a promising prospect for the treatment of various inflammatory diseases, including OA.