Guoliang Wang, Jie Liu, Peiyi Bai, Hong Jiao, Xiaohui Kong, Zhangke Guo, Gaopeng Li, Aijun Liu
Beijing Children’s Hospital, Beijing Pediatric Research Institute, Capital Medical University and National Center for Children’s Health. Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences and Tongji Shanxi Hospital. General Hospital of Taiyuan Iron and Steel Group Company and Sixth Hospital of Shanxi Medical University. Tongji Shanxi Hospital and Third Hospital of Shanxi Medical University. Beijing Chaoyang Hospital.
China
Journal of Nanobiotechnology
J Nanobiotechnology 2026;
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.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Animal Models of Pulmonary Vascular Disease and Therapy
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes