Inhalable extracellular vesicle delivered IL-10 mRNA attenuates pulmonary hypertension in rats

  • J Nanobiotechnology. 2026 Jun 23. doi: 10.1186/s12951-026-04723-5.
Guoliang Wang  #  1 ,  Jie Liu  #  2  3 ,  Peiyi Bai  4  5 ,  Hong Jiao  6 ,  Xiaohui Kong  6 ,  Zhangke Guo  7 ,  Gaopeng Li  8 ,  Aijun Liu  9  10
Affiliations
  • 1. Department of Tumor and Immunology, Beijing Children's Hospital, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children's Health, Beijing, 100045, China. [email protected].
  • 2. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 3. Department of Respiratory Medicine, Capital Medical University, Beijing, 100069, China.
  • 4. Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
  • 5. Burns Department, General Hospital of Taiyuan Iron and Steel Group Co., Ltd, Sixth Hospital of Shanxi Medical University, Taiyuan, 030009, China.
  • 6. Department of Tumor and Immunology, Beijing Children's Hospital, Beijing Pediatric Research Institute, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
  • 7. Department of Cardiac Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
  • 8. Department of Hepatobiliary Surgery, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
  • 9. Department of Cardiac surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. [email protected].
  • 10. Heart Center, Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 42337573 DOI: 10.1186/s12951-026-04723-5
Abstract

Pulmonary hypertension is a lethal condition characterized by an enhanced inflammatory response in the lungs. Cytokines such as interleukin-10 (IL-10) have demonstrated considerable potential as potent inflammation suppressors. Especially, with pulmonary hypertension patients showing diminished IL-10 levels. However, off-target toxicity poses a major limitation to their applications. Here we report a strategy in which IL-10 mRNA, encapsulated in extracellular vesicles, is delivered by inhalation. Targeted delivery to lung with preferential uptake reduces systemic side effects. IL-10 mRNA exerts selective immunomodulatory effects by suppressing inflammatory cytokine secretion and promoting Apoptosis in M1-like pulmonary macrophages while sparing M2-like macrophages. This macrophage subset-specific regulation reshapes the pulmonary cytokine microenvironment, significantly down-regulating factors that promote pulmonary hypertension progression and ultimately inhibiting disease progression. The strategy was demonstrated in the sugen5416/hypoxia-induced rat model of pulmonary hypertension, providing substantial protection against disease progression. This shows the potential for locally delivered cytokine-based immunosuppressive therapies for inflammatory lung diseases.

Keywords
Extracellular vesicle; Interleukin-10; Macrophage; Pulmonary hypertension.
Products