已传文件：photo/1773121782.png
Diabetic chronic wounds are a devastating complication faced by hundreds of millions of patients worldwide. The core pathological feature is the persistent pro-inflammatory microenvironment that makes the wounds difficult to heal. Recent studies have found that excessive accumulation of reactive oxygen species (ROS) and abnormal accumulation of lactic acid are key factors maintaining local chronic inflammation. Lactic acid not only damages mitochondrial function and metabolic homeostasis but also drives histone lactylation modification, reprogramming the transcriptional network to maintain the inflammatory state. Traditional treatments are difficult to simultaneously intervene in metabolic disorders and epigenetic abnormalities, resulting in limited efficacy. Natural lactic acid oxidase (LOX) provides a proof-of-concept for targeted lactate therapy, but its instability and high cost limit its clinical application. Single-atom nanoenzymes (SAzymes) have become a research hotspot in the field of catalysis due to their atom-level dispersed active sites, maximum metal utilization efficiency, and clear coordination environment. However, the existing nanoenzyme platforms lack the precise geometry and electronic structure required for lactate dehydrogenation under physiological conditions. Recently, a team led by Professor Liu Nanxin and Chen Tao from the Affiliated Stomatological Hospital of Chongqing Medical University published a significant study in ACS Nano, developing a phosphorus-doped single-atom iron nanozyme (Fe@CN-P), which successfully overcame the long-standing challenge of metal-based nanoenzymes in lactate oxidation. This nanozyme achieves the dual functions of lactate "reversal-reutilization" through atomic-level electron structure engineering, simultaneously regulating metabolic reprogramming and epigenetic remodeling, effectively eliminating ROS, inhibiting inflammation, promoting vascular regeneration, and significantly accelerating the healing of diabetic infected wounds.
Key analysis
Core highlights of the research:
1. The designed and synthesized Fe@CN-P has broken through the technical bottleneck of metal-based nanoenzymes in lactate oxidation;
2. Achieving pH-responsive intelligent switching of enzyme activity, acidic antibacterial and neutral anti-inflammatory, adapting to the pathological microenvironment changes of diabetic wounds;
3. Proposing a new regulatory strategy of "lactate-reutilization", achieving the dual functions of catalytic oxidation of lactate and energy reutilization of pyruvate;
4. Revealing the epigenetic regulatory axis of "lactic acid-H3K18la-FGR/IL-1α/MMP9", achieving coordinated intervention of metabolism and epigenetics;
5. In vitro and in vivo experiments have confirmed that Fe@CN-P effectively treats diabetic chronic infected wounds through antibacterial, anti-inflammatory, metabolic reprogramming, epigenetic remodeling, and promoting angiogenesis, achieving efficient treatment.
DOI：10.1021/acsnano.5c20192
