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

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

  • Int J Nanomedicine. 2025 Oct 27:20:12993-13006. doi: 10.2147/IJN.S545569.
Qingyan Li # 1,  Weilin Zheng # 2,  Jingge Cheng # 1,  Bo Li 1,  Yutian Lei 1,  Huilong Guo 1,  Youshan Xv 3,  Jiaming Huang 4,  Xiaoxing Liao 1 5
Affiliations

Affiliations

  • 1 Emergency and Disaster Medicine center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong Province, People's Republic of China.
  • 2 Department of Hepatobiliary and Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People's Republic of China.
  • 3 The Huiqiao Medical Center (International Medical Service) of Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
  • 4 Department of Hepatobiliary and Gastrointestinal Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong Province, People's Republic of China.
  • 5 The Institute of Emergency Care and Resuscitation, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong Province, People's Republic of China.
  • # Contributed equally.
PMID: 41179976 DOI: 10.2147/IJN.S545569
Abstract

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.

Keywords

ROS-scavenge; anti-inflammatory microenvironment; apoptosis; diabetic wound; nanoenzyme.

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