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

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-024-02721-z
Popis: 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.
Databáze: Directory of Open Access Journals
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