Inhaled siRNA nanoparticles targeting IL11 inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge
Document Type
Article
Publication Date
6-1-2022
Abstract
Interleukin-11 (IL-11) is a profibrotic cytokine essential for the differentiation of fibroblasts into collagen-secreting, actin alpha 2, smooth muscle–positive (ACTA2+) myofibroblasts, driving processes underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we developed an inhalable and mucus-penetrative nanoparticle (NP) system incorporating siRNA against IL11 (siIL11@PPGC NPs) and investigated therapeutic potential for the treatment of IPF. NPs are formulated through self-assembly of a biodegradable PLGA-PEG diblock copolymer and a self-created cationic lipid-like molecule G0-C14 to enable efficient transmucosal delivery of siIL11. Noninvasive aerosol inhalation hindered fibroblast differentiation and reduced ECM deposition via inhibition of ERK and SMAD2. Furthermore, siIL11@PPGC NPs significantly diminished fibrosis development and improved pulmonary function in a mouse model of bleomycin-induced pulmonary fibrosis without inducing systemic toxicity. This work presents a versatile NP platform for the locally inhaled delivery of siRNA therapeutics and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including IPF.
Identifier
85132604356 (Scopus)
Publication Title
Science Advances
External Full Text Location
https://doi.org/10.1126/sciadv.abn7162
e-ISSN
23752548
PubMed ID
35731866
Issue
25
Volume
8
Grant
TMSK-2020-008
Fund Ref
National Science Foundation
Recommended Citation
Bai, Xin; Zhao, Guolin; Chen, Qijing; Li, Zhongyu; Gao, Mingzhu; Ho, William; Xu, Xiaoyang; and Zhang, Xue Qing, "Inhaled siRNA nanoparticles targeting IL11 inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge" (2022). Faculty Publications. 2918.
https://digitalcommons.njit.edu/fac_pubs/2918

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