Journal of Nanobiotechnology (Jul 2024)

Nebulized milk exosomes loaded with siTGF-β1 ameliorate pulmonary fibrosis by inhibiting EMT pathway and enhancing collagen permeability

  • Chong Qiu,
  • Zhenyu Zhao,
  • Chenglin Xu,
  • Ranran Yuan,
  • Yuxuan Ha,
  • Qingchao Tu,
  • Houqian Zhang,
  • Zhen Mu,
  • Quanlin Xin,
  • Yu Tian,
  • Aiping Wang,
  • Hongbo Wang,
  • Yanan Shi

DOI
https://doi.org/10.1186/s12951-024-02721-z
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 16

Abstract

Read online

Abstract Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-β1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-β1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-β1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-β1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.

Keywords