Trimanganese Tetroxide Nanozyme protects Cartilage against Degeneration by Reducing Oxidative Stress in Osteoarthritis

Abstract

Osteoarthritis, a chronic degenerative cartilage disease, is the leading cause of movement disorders among humans. Although the specific pathogenesis and associated mechanisms remain unclear, oxidative stress-induced metabolic imbalance in chondrocytes plays a crucial role in the occurrence and development of osteoarthritis. In this study, a trimanganese tetroxide (Mn 3 O 4 ) nanozyme with superoxide dismutase (SOD)-like and catalase (CAT)-like activities is designed to reduce oxidative stress-induced damage and its therapeutic effect is investigated. In vitro, Mn 3 O 4 nanozymes are confirmed to reprogram both the imbalance of metabolism in chondrocytes and the uncontrolled inflammatory response stimulated by hydrogen peroxide. In vivo, a cross-linked chondroitin sulfate (CS) hydrogel is designed as a substrate for Mn 3 O 4 nanozymes to treat osteoarthritis in mouse models. As a result, even in the early stage of OA (4 weeks), the therapeutic effect of the Mn 3 O 4 @CS hydrogel is observed in both cartilage metabolism and inflammation. Moreover, the Mn 3 O 4 @CS hydrogel maintained its therapeutic effects for at least 7 days, thus revealing a broad scope for future clinical applications. In conclusion, these results suggest that the Mn 3 O 4 @CS hydrogel is a potentially effective therapeutic treatment for osteoarthritis, and a novel therapeutic strategy for osteoarthritis based on nanozymes is proposed.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

“…S@M@H NPs possessed great potential for diabetic wound treatment. These findings also highlighted the potential of S@M@H NPs as a candidate for therapeutic agent not only for chronic wound healing but also for other ROS-meditated inflammatory disease, like osteoarthritis, acute kidney injury and inflammatory bowel disease [ 59 – 61 ]. In Wang’s study, manganese tetroxide nanozyme with both SOD and CAT like activity were successfully applied to treat osteoarthritis.…”

“…In Wang’s study, manganese tetroxide nanozyme with both SOD and CAT like activity were successfully applied to treat osteoarthritis. More importantly, a cross-linked chondroitin sulfate hydrogel is designed as a carrier to realize the prolonged-release of nanozyme [ 61 ]. Similarly, hydrophobic Mn 3 O 4 nanoparticles were loaded inside PTC micelles to prevent premature release during circulation in Hong’s work to treat acute kidney injury [ 60 ].…”

Organic–inorganic composite hydrogels: compositions, properties, and applications in regenerative medicine

“…Oxidative stress-induced imbalance in chondrocyte metabolism plays a crucial role in the progression of osteoarthritis. To mitigate damage caused by oxidative stress, Wang et al 241 employed crosslinked chondroitin sulfate hydrogels loaded with manganese dioxide NPs (Mn 3 O 4 ) and injected the hydrogel into the joint cavity. This study indicate that manganese oxide enzymes can decrease intracellular levels of ROS in chondrocytes by emulating the functions of superoxide dismutase (SOD) and catalase (CAT).…”

Construction of Mn–N–C nanoparticles with multienzyme-like properties and photothermal performance for the effective treatment of bacterial infections

“…22 Mn is one of the key elements in organisms, and as an essential cofactor of numerous metalloenzymes, it plays a critical role in regulating functions of enzymes, which affects the normal metabolism and intracellular redox homeostasis. Various Mn-based nanozymes have different enzyme-like activities, such as catalase-like (CAT-like), 23 superoxide dismutase-like (SOD-like), 24 oxidase-like (OXD-like) 25 and POD-like activities. 26 Many nanozymes exhibit single-modal catalytic activity, thus failing to achieve synergistic antioxidant effects, but avoid the side effects of reactive oxygen species (ROS).…”