Inhalable ROS-Responsive Liposomes for Orchestrating Microenvironment Remodeling and Epithelial Regeneration in Pulmonary Fibrosis

• • The SAB/GC-1@Lip-cRGD liposomes reduced the proportion of CD206+ M2 macrophages from 27.4% (model group) to 6.2% (treated group), a 77.4% reduction, demonstrating potent immunomodulatory effects that are critical for halting fibrosis progression. • • Treatment with SAB/GC-1@Lip-cRGD significantly decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and the pro-fibrotic cytokine TGF-β1 in both bronchoalveolar lavage fluid and lung homogenates, confirming effective suppression of the inflammatory and fibrotic cascade. • • The ROS-responsive liposomal system enables targeted delivery and controlled release of therapeutic agents specifically within the high-ROS fibrotic microenvironment, enhancing drug accumulation at fibrotic lesions while minimizing systemic toxicity—a key advantage over conventional systemic therapies. • • The combination of SAB (antioxidant) and GC-1 (TRβ agonist) synergistically remodels the fibrotic niche and promotes epithelial regeneration, leading to significant collagen depletion and restoration of alveolar integrity, as evidenced by superior anti-fibrotic efficacy compared to single-drug or non-targeted formulations.