Inhaled siRNA nanoparticles targeting <i>IL11</i> inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35731866.
- Also identified by DOI 10.1126/sciadv.abn7162 and PMC identifier 9216512.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup>) 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 <i>IL11</i> (si<i>IL11</i>@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 si<i>IL11</i>. Noninvasive aerosol inhalation hindered fibroblast differentiation and reduced ECM deposition via inhibition of ERK and SMAD2. Furthermore, si<i>IL11</i>@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.
Medical subject headings
- Idiopathic Pulmonary Fibrosis
- Nanoparticles