Inhalable Acid-Responsive Methane Nanocapsule for Remodeling Fibrogenic Microenvironment to Alleviate Idiopathic Pulmonary Fibrosis

• • MNC inhalation achieved efficient lung deposition and sustained methane release in a bleomycin-induced pulmonary fibrosis model, significantly reducing inflammation and fibrosis while improving lung function without systemic side effects (Jin et al., 2026). • • The acid-responsive methane prodrug Fe(BPY)2(CH3)2 enables spatiotemporally controlled methane release in acidic inflammatory niches, facilitating mucosal penetration and sustained release (Jin et al., 2026). • • MNC rebalances macrophage polarization by inhibiting M2 phenotype overexpression and downregulates the MMP9/TIMP-1 ratio, suppressing myofibroblast proliferation and EMT (Jin et al., 2026). • • The nanocapsule is formulated from biodegradable PLGA-PEG copolymer, ensuring biocompatibility and potential for clinical translation in inhalable gas therapy (Jin et al., 2026).