Mitochondria‐targeting Bimetallic Cluster Nanozymes Alleviate Neuropathic Pain Through Scavenging ROS and Reducing Inflammation

Neuropathic pain is a significant public health concern. Inflammatory mediators and reactive oxygen species (ROS) are recognized as primary contributors to pain perception. In this study, a mitochondria-targeted modification of bimetallic cluster nanozyme (TPP-Au-Ru) is developed. This TPP-Au-Ru nanozyme exhibits a high affinity for the mitochondrial matrix, effectively scavenging ROS and attenuating inflammatory mediators in both in vitro and in vivo settings. Additionally, the nanozyme inhibits the activation of the MAPK and NF-κB signaling cascades and protect mitochondrial function. Furthermore, a therapeutic dose of the TPP-Au-Ru nanozyme is able to alleviate nociceptive symptoms for up to 36 h with minimal biological toxicity. Therefore, the sustained mitochondrial delivery of TPP-Au-Ru nanozyme provides an effective and long-lasting approach to neuropathic pain. This innovative approach shows promise for the development of more efficient therapeutic interventions, potentially revolutionizing the management of neuropathic pain and enhancing the quality of life for affected individuals.