MXenzyme Nanotherapeutics for Oxidative Stress‐Associated Myopathies Remission

Abstract Disruption of redox homeostasis, primarily due to inadequate endogenous antioxidant defenses, has been increasingly identified as a pivotal contributor to the pathogenesis of skeletal muscle injury, with excessive accumulation of reactive oxygen species (ROS) acting as a key pathological mediator. Consequently, the effective elimination of surplus ROS in skeletal muscle has emerged as an efficient therapeutic strategy for alleviating muscle damage. In this study, a specific ultrathin 2D niobium carbide (Nb ₂ C) MXene with multienzyme‐mimicking capabilities, termed Nb ₂ C MXenzyme, designed to combat skeletal muscle injury by efficiently scavenging ROS and promoting myogenesis, is engineered. This biocompatible Nb ₂ C MXenzyme mimics the activities of several antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase, and peroxidase, providing a comprehensive approach to oxidative stress mitigation. The Nb ₂ C MXenzyme not only protects muscle cells from oxidative damage but also activates the IGF1/IGFBP4 signaling pathway, thereby restoring muscle contractile function and enhancing myogenesis. These therapeutic effects are systematically validated in a mouse model of skeletal muscle oxidative stress induced by chronic intermittent hypoxia. The findings highlight the potential and feasibility of Nb ₂ C MXenzyme as an innovative therapeutic strategy for skeletal muscle repair and underscore its promise for clinical translation in treating oxidative stress‐related muscle pathologies.