Dual-Functional PDA@Au/CeO₂ Nanozymes Enable CT Tracking and Potent Antifibrotic MSC Therapy

Pulmonary fibrosis is a debilitating lung disease for which effective therapies remain limited. In this study, we developed a mesenchymal stem cell (MSC)-based delivery system incorporating PDA@Au/CeO₂ nanoparticles (MSCs-PDA@Au/CeO₂/NT) for targeted antifibrotic therapy and imaging guidance. PDA@Au/CeO₂ nanoparticles showed excellent biocompatibility, efficient MSC uptake, and superior CT imaging performance. In TGF-β1-induced fibroblast models, the composite system markedly inhibited myofibroblast differentiation, suppressed ROS accumulation, and selectively induced apoptosis of aberrantly activated fibroblasts while preserving MSC viability. In bleomycin-induced pulmonary fibrosis mice, MSCs-PDA@Au/CeO₂/NT significantly improved lung architecture and function, decreased collagen deposition, and modulated the immune microenvironment by downregulating fibrosis-related signaling pathways. Biosafety assessments confirmed no significant systemic toxicity. This study demonstrates a safe and effective nanomaterial-assisted stem cell strategy for pulmonary fibrosis treatment and potential clinical translation.