Enhanced Pulmonary Fibrosis Treatment by Self-Assembling Peptide Nanofibers via Improved Pulmonary Delivery and Retention

Abstract Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease, which progressively impairs pulmonary function, with limited therapeutic options available. In this study, we designed CQ7, a self-assembling peptide that integrates a therapeutic peptide with a self-assembly motif. CQ7 monomers spontaneously form supramolecular nanofibers under physiological conditions, both extracellularly and intracellularly. This nanofiber structure promotes efficient lung retention and targeted pulmonary delivery, leading to enhanced anti-fibrotic efficacy. We evaluated the anti-fibrotic and anti-inflammatory effects of CQ7 in a murine PF model via both intraperitoneal and inhalation administrations. Transcriptomic sequencing and experimental validation further revealed that CQ7 may act through the regulation of mitochondrial function, reducing cellular oxidative stress and thereby regulating the apoptosis process. Collectively, this work demonstrates a novel peptide-based strategy with significant potential for improving PF outcomes and clinical translation.