2. Academic Validation
  3. D-Mannose-Modified M2 Macrophage Membrane-Derived Decoy Nanovesicles for Synergistic Immunotherapy of Asthma

D-Mannose-Modified M2 Macrophage Membrane-Derived Decoy Nanovesicles for Synergistic Immunotherapy of Asthma

  • ACS Nano. 2025 Dec 24. doi: 10.1021/acsnano.5c04996.
Shukun Zhao 1 2,  Qiong Jiang 1,  Ling Yu 3,  Quan Liu 4,  Zi Chen 5,  Danting Zhan 1,  Shuyu Chen 1,  Yuqiong Yang 6,  Jiacheng Zhong 1,  Bingxin Guo 1,  Fei Shi 1 7,  Rongchang Chen 1 6 8,  Lingwei Wang 1,  Lang Rao 2,  Junxia Zheng 9 10,  Qian-Fang Meng 2,  Shanze Chen 1 10 11
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen Clinical Research Center for Respiratory Disease, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen 518020, China.
  • 2 Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
  • 3 State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
  • 4 Medical laboratory center, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen University, Shenzhen 518052, China.
  • 5 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
  • 6 National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  • 7 Department of Infectious Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong 518020, China.
  • 8 Hetao Institute of Guangzhou National Laboratory, Shenzhen 518132, China.
  • 9 School of Biomedical and Pharmaceutical Science, Guangdong University of Technology, Guangzhou 510006, China.
  • 10 Institute for Safflower Industry Research, Key Laboratory of Xinjiang Phytomedicine Resource and Utilization (Ministry of Education), School of Pharmacy, Shihezi University, Xinjiang 832003, China.
  • 11 College of Pharmacy, The Second Clinical Medical College (Shenzhen People's Hospital), The Fifth Affiliated Hospital, Jinan University, Guangzhou 510632, China.
PMID: 41441854 DOI: 10.1021/acsnano.5c04996
Abstract

Eosinophilic asthma is a chronic inflammatory disease driven by Type 2 immune cells and cytokines. While cytokine-based immunotherapies have shown promising efficacy in asthma treatment, current approaches often fail to simultaneously target multiple cytokines. In this study, we present nanodecoys derived from the cellular membranes of M2 macrophages, which exhibit a high density of Cytokine Receptors, enabling efficient sequestration of multiple Type 2 cytokines. This mechanism significantly alleviates OVA-induced eosinophilic asthma inflammation in mice. To enhance therapeutic efficacy, D-mannose glycans, a potential immunoregulatory molecule for asthma, were modified onto the surface of the nanovesicles. This modification facilitates the phagocytic clearance of absorbed cytokines by targeting the Mannose Receptor (CD206). Consequently, the mannose-modified nanovesicles exhibit synergistic immunosuppressive effects on asthmatic inflammation by inhibiting M2 macrophage polarization, CD4+ T cell Th2 polarization, and eosinophil activation, as revealed by single-cell RNA Sequencing and in vitro analyses. In summary, this study presents a safe and effective nanotechnology-based immunotherapy for asthma and potentially Other Type 2 inflammatory diseases.

Keywords

biomaterials; drug delivery; eosinophilic asthma; extracelluar vesicles; immunotherapy; nanodecoys.

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