Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis

Osteoarthritis (OA) is always characterized as excessive reactive oxygen species (ROS) inside articular cavity. Mimicking natural metalloenzymes with metal ions as the active centers, stable metal organic framework (MOF) formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases. Herein, a series of novel copper-morin-based MOF (CuMHs) with different molar ratios of Cu²⁺ and MH were employed to serve as ROS scavengers for OA therapy. As a result, CuMHs exhibited enhanced dispersion in aqueous solution, improved biocompatibility, and efficient ROS-scavenging ability compared to MH. On the basis of H₂O₂-stimulated chondrocytes, intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu₆MH (Cu²⁺ and MH molar ratio of 6:1). Meanwhile, Cu₆MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6, MMP13, and MMP3, and up-regulating cartilage specific gene expression as well. Importantly, Cu₆MH could repair mitochondrial function by increasing mitochondrial membrane potential, reducing the accumulation of calcium ions, as well as promoting ATP content production. In OA joint model, intra-articular (IA) injected Cu₆MH suppressed the progression of OA. It endowed that Cu₆MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.