Shuhong Guan, Yiwen Yao, Yu Ding, Long Zhang, Junkang Huangfu, Xiyao Chen, Xiaoyu Wang, Jun Zhou
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/CeO 2 nanoparticles (MSCs-PDA@Au/CeO 2 /NT) for targeted antifibrotic therapy and imaging guidance. PDA@Au/CeO 2 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/CeO 2 /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.