Engineering Multifunctional Nanozymes to Reprogram Oxidative Stress and Inflammation in Chronic Wounds.

Introduction: Diabetic wounds represent a growing clinical challenge worldwide, characterized by persistent immune dysregulation and excessive inflammation that lead to impaired healing and chronic progression. Methods: To address this, we developed a composite nanosystem, termed Ru@ACEI, composed of ruthenium-incorporated hollow mesoporous silica nanoparticles loaded with angiotensin-converting enzyme inhibitors (ACEIs). Results: The Ru@ACEI nanoparticles exhibit dual enzyme-mimetic activities (superoxide dismutase and catalase), effectively scavenging excess reactive oxygen species (ROS). This activity reduces cellular apoptosis and promotes endothelial cell proliferation. Following cellular uptake, Ru@ACEI catalyzes the decomposition of peroxides into water and oxygen, thereby suppressing the NLRP3/Caspase-3/Caspase-9 apoptosis pathway. The consequent improvement in endothelial cell survival helps reverse local hyperinflammation in diabetic wounds. Conclusion: Collectively, these findings demonstrate that the Ru@ACEI nanosystem accelerates diabetic wound healing by mitigating the inflammatory microenvironment and downregulating the expression of pro-inflammatory factors, offering a promising therapeutic strategy for managing chronic diabetic wounds.