A pH-Responsive Ceria-Supported Iridium Clusterzyme for Combined Antibacterial and Anti-inflammatory Therapies in Diabetic Wound Healing.

Abstract

The treatment of diabetic wounds is hindered by multiple factors, including Staphylococcus aureus (S. aureus) biofilms (the predominant pathogen in diabetic wound infections), dysregulated immune responses, and insufficient angiogenesis. The complex interactions among these local pathological factors have been insufficiently addressed in the development of existing therapeutic approaches. This study reports a hybrid biocatalytic platform consisting of abundant iridium (Ir) clusters supported on ceria (Ir-CeO2). This architectural configuration enables pH-responsive reactive oxygen species (ROS) catalysis, allowing the biocatalyst to exert concurrent antimicrobial and anti-inflammatory effects, which collectively promote healing of diabetic wounds. Ir-CeO2 displays dual pH-dependent ROS modulation: ROS generation under acidic conditions and ROS scavenging under neutral pH. In S. aureus-infected environments, the biocatalyst exerts potent antibacterial effects via catalytic ROS production. Following pathogen clearance, Ir-CeO2 continues to play a bifunctional role by alleviating oxidative stress in inflamed wounds, promoting the polarization of macrophages toward the M2 phenotype-a critical event for accelerating wound healing. Collectively, these results highlight the multifaceted therapeutic efficacy of Ir-CeO2, which seamlessly integrates potent antibacterial activity against S. aureus infections with anti-inflammatory and pro-angiogenic functions. This synergistic profile establishes Ir-CeO2 as a highly promising agent for the holistic management of complicated diabetic ulcers, thereby addressing key shortcomings of existing treatment modalities.