A Highly Efficient and Biocompatible Cupper-Based Single-Atom Nanocatalyst with Unsaturated Coordination Structure for Efficient Diabetic Wound Healing

The unsaturated coordination alters the electronic structure of metal atoms, exposing more active sites, and thereby demonstrating high catalytic activity. It is extremely difficult to precisely regulate the unsaturated coordination environment of single-atom catalysts due to the thermodynamically unstable structure. Herein, a facile “micelle-confined oxidative crosslinking and coupled coordination” strategy is proposed to construct a copper single-atom catalyst with an unsaturated Cu-N 2 coordination structure in a confined silica-carbon framework (Cu SA@MCSN), which demonstrate unique pH-dependent multiple-enzymatic activity (peroxidase (POD)-like activity in an acidic environment with a low K m of 6.9 mM and V max of 6.3 × 10 −8 M s −1 and superoxide dismutase (SOD)- and catalase (CAT)-like activity under neutral conditions). Density functional theory calculations also further confirm that the asymmetric Cu-N 2 sites with edge configurations exhibit a strong adsorption capacity for oxygen-containing intermediates showing a faster reaction rate compared to their saturated coordination structure. More importantly, the metformin (MET)-loaded Cu SA@MCSN demonstrates multi-pathway antibacterial ability in acidic microenvironments and long-term anti-inflammatory effects in neutral microenvironments through the downregulation of pro-inflammatory factors and the up-regulation of anti-inflammatory and tissue regeneration factors on a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds.