Macrophage-mimetic photothermal nanotherapeutics regulate mitochondrial homeostasis and inflammatory cascades in lung ischemia-reperfusion injury

  • Cell Rep Med. 2026 May 19;7(5):102768. doi: 10.1016/j.xcrm.2026.102768.
Haoxiang Yuan  1 ,  Bo Zeng  2 ,  Pu Shen  3 ,  Jiancheng Deng  4 ,  Ying Chen  4 ,  Meiyu Huang  4 ,  Wentao Wu  4 ,  Xin Xu  4 ,  Xuanlin Zhang  4 ,  Xue Liu  5 ,  Xudong Zhang  6 ,  Zhijin Fan  7 ,  Jianxing He  8
Affiliations
  • 1. Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China; Institute for Engineering Medicine, Kunming Medical University, Kunming 650500, China.
  • 2. Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • 3. Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • 4. Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • 5. Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Innovative Molecular Imaging, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523018, China.
  • 6. Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen 518107, China. Electronic address: [email protected].
  • 7. Institute for Engineering Medicine, Kunming Medical University, Kunming 650500, China. Electronic address: [email protected].
  • 8. Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China; Southern Medical University, Guangzhou 510120, China. Electronic address: [email protected].
PMID: 42030937 DOI: 10.1016/j.xcrm.2026.102768
Abstract

Pulmonary ischemia-reperfusion injury is a major cause of acute lung injury and primary graft dysfunction after lung transplantation, with few effective treatments available. In this study, we develop a macrophage-membrane-coated mesoporous polydopamine nanoparticle system loaded with ginsenoside Rg3 (Rg3@PACVs) and activated by near-infrared irradiation. This design enables precise targeting of injured lung tissue via chemokine-receptor- and integrin-mediated pathways, while allowing controllable, on-demand drug release. In vitro hypoxia-reoxygenation models and a rat pulmonary ischemia-reperfusion model demonstrate that Rg3@PACVs with mild photothermal therapy reduce Reactive Oxygen Species accumulation, suppress inflammatory cytokines, preserve mitochondrial structure and tricarboxylic acid cycle metabolism, and alleviate tissue injury. The approach combines targeted delivery, multimodal protection against oxidative and inflammatory damage, and mitochondrial restoration. These findings suggest a promising therapeutic strategy for mitigating lung ischemia-reperfusion injury and potentially for Other inflammation- and oxidative-stress-driven pulmonary diseases.

Keywords
ginsenoside Rg3; ischemia-reperfusion injury; macrophage membrane; mesoporous polydopamine; mild thermotherapy; mitochondrial homeostasis.
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