Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that leads to interstitial inflammation, lung damage, and eventually life-threatening complications. Among various pathologic factors, Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF. It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes.

Inhaled RNA drugs to treat lung diseases: Disease-related cells and nano-bio interactions.

In recent years, RNA-based therapies have gained much attention as biomedicines due to their remarkable therapeutic effects with high specificity and potency. Lung diseases offer a variety of currently undruggable but attractive targets that could potentially be treated with RNA drugs. Inhaled RNA drugs for the treatment of lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome, have attracted more and more attention.

Airway epithelial cell-specific delivery of lipid nanoparticles loading siRNA for asthma treatment.

With specific and inherent mRNA cleaving activity, small interfering RNA (siRNA) has been deemed promising therapeutics to reduce the exacerbation rate of asthma by inhibiting the expression and release of proinflammatory cytokines from airway epithelial cells (AECs). To exert the therapeutic effects of siRNA drugs, nano-formulations with high efficiency and safety are required to deliver these nucleic acids to the target cells. Herein, we exploited novel inhaled lipid nanoparticles (LNPs) targeting intercellular adhesion molecule-1 (ICAM-1) receptors on the apical side of AECs.