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Updated: Jan 8, 2026
In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model
Published on: November 17, 2018
Mitochondrial-Targeting Drug-Loaded Nanoparticles Reprogram Macrophage Metabolism via ROS/NO Co-elimination for
Xuan Zhou1, Zhidan Huang1, Huake Yang1
1Department of Plastic and Cosmetic Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing 400038, China.
Abstract:
Diabetic wounds pose a growing healthcare challenge, characterized by heavy M1 macrophage infiltration, reactive oxygen species (ROS) overproduction, tissue hypoxia, and cytokine storms. The diabetic microenvironment fails to support the critical M1-to-M2 macrophage phenotypic switch, trapping tissues in persistent pathological inflammation that disrupts natural healing processes. In this study, we developed triphenylphosphonium (TPP)-modified mitochondria-targeting nanoparticles, where liposomes encapsulated two metabolomically guided agents: aminooxyacetic acid (AOAA) to suppress nitric oxide (NO) production and hollow mesoporous manganese dioxide (H-MnO2) to scavenge mitochondrial ROS and supply O2. In vitro, after successful mitochondrial internalization by macrophages, the nanoparticles reduced NO and ROS levels, enhanced mitochondrial respiration, and reprogrammed macrophage metabolism─shifting from aerobic glycolysis to oxidative phosphorylation (OXPHOS). This metabolic shift drove macrophage transition from pro-inflammatory M1 to anti-inflammatory M2 and thus resolved aberrant inflammation. In diabetic murine wound models, TPP-L@H-MnO2@AOAA further validated its efficacy. By modulating macrophage repolarization, it promoted re-epithelialization and collagen deposition. Overall, these anti-inflammatory nanoparticles with sustained-release capability provide a promising therapeutic tool for clinical management of diabetic wounds.
Insights
New nanoparticles reprogram macrophages to resolve inflammation and promote healing in diabetic wounds. This approach targets mitochondrial dysfunction, shifting macrophages from a pro-inflammatory to an anti-inflammatory state for improved wound repair.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Wound Healing Research
Background:
- Diabetic wounds exhibit M1 macrophage dominance, reactive oxygen species (ROS) overproduction, and hypoxia, hindering natural healing.
- The diabetic microenvironment impedes the crucial M1-to-M2 macrophage switch, leading to chronic inflammation.
- Current treatments struggle to address the complex inflammatory milieu of diabetic wounds.
Purpose of the Study:
- To develop mitochondria-targeting nanoparticles for treating diabetic wounds.
- To reprogram macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2.
- To investigate the therapeutic potential of these nanoparticles in diabetic wound models.
Main Methods:
- Developed triphenylphosphonium (TPP)-modified liposomes encapsulating aminooxyacetic acid (AOAA) and hollow mesoporous manganese dioxide (H-MnO2).
- Assessed nanoparticle internalization, NO and ROS scavenging, and metabolic reprogramming (aerobic glycolysis to oxidative phosphorylation) in macrophages.
- Evaluated therapeutic efficacy in diabetic murine wound models, focusing on re-epithelialization and collagen deposition.
Main Results:
- Nanoparticles successfully targeted macrophage mitochondria, reducing nitric oxide (NO) and ROS levels.
- Macrophages exhibited enhanced mitochondrial respiration and a metabolic shift towards oxidative phosphorylation (OXPHOS).
- This reprogramming promoted M1-to-M2 macrophage transition, resolving inflammation and accelerating wound healing, including improved re-epithelialization and collagen deposition.
Conclusions:
- TPP-modified nanoparticles effectively reprogram macrophage metabolism and phenotype, resolving inflammation in diabetic wounds.
- The developed nanoparticles demonstrate significant therapeutic potential for managing diabetic wound healing.
- This nanomedicine approach offers a promising strategy for clinical applications in chronic wound care.
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