Hydrogen-induced disruption of the airway mucus barrier enhances nebulized RNA delivery to reverse pulmonary fibrosis.

Summary

A hydrogen-augmented aerosol device and hybrid lipid nanoparticles enabled efficient macrophage transfection and induced hepatocyte growth factor to repair lung tissue, reversing pulmonary fibrosis in vivo. Hydrogen flow altered mucus–nanoparticle interactions to boost airway deposition at low LNP doses.

Key Findings

• A nose-only aerosol device integrated with therapeutic hydrogen enabled precise low-dose LNP administration and high lung macrophage transfection.
• Hybrid lipid nanoparticles combining charge-inverting lipid films with apoptotic T-cell membranes enhanced endosomal escape and induced HGF production.
• Hydrogen flow-induced shear disrupted nanoparticle–mucus interactions, increasing airway deposition and reversing pulmonary fibrosis in vivo.

Clinical Implications

If translated, hydrogen-assisted aerosolized RNA delivery could enable low-dose, lung-targeted gene therapies for fibrotic lung disease and other airway disorders with thick mucus.

Limitations

• Preclinical work; safety and dosing windows in humans remain unknown
• Durability and repeat-dosing effects of hydrogen-assisted delivery need clinical evaluation

Future Directions

First-in-human studies to evaluate safety, tolerability, and pharmacodynamics; explore indications beyond fibrosis (e.g., CF, COPD) and payloads (mRNA/siRNA/CRISPR).