Analysis of the therapeutic effect and potential mechanism of Fe3O4-polydopamine nanoparticles in enhancing mesenchymal stem cells therapy for pulmonary fibrosis

Pulmonary fibrosis (PF) is a chronic lung disease characterized by progressive fibrosis and scar tissue formation, often leading to respiratory failure. Current treatments are limited to alleviating symptoms and slowing disease progression. Mesenchymal stem cells (MSC) can be applied to treat PF owing to their anti-inflammatory, immunomodulatory, tissue repair, and vascular regeneration properties. However, the short pulmonary retention time of intravenously injected MSC limits therapeutic efficacy. We combined MSC with Fe₃O₄-polydopamine (Fe₃O₄@PDA) nanoparticles and applied an external magnetic field to guide magnetized MSC to damaged lung areas. This strategy not only enhances MSC localization, targeting, and retention but also amplifies their therapeutic effects by activating critical therapeutic molecules involved in MSC migration, adhesion, homing, and intercellular connections, as well as signaling pathways such as MAPK/AKT. <i>In vivo</i> studies using a PF mouse model demonstrated that Fe₃O₄@PDA-magnetized MSC therapy effectively alleviated lung tissue fibrosis and significantly reduced the expression of inflammatory factors. RNA sequencing analysis revealed profound changes in gene expression profiles, particularly in pathways such as ECM-receptor interactions, focal adhesion, and the TGF-β pathway. Compared to non-magnetized MSC therapy, magnetized MSC therapy significantly activated essential signaling pathways in lung tissues, including cell adhesion molecules, leukocyte transendothelial migration, and the Rap1 signaling pathway. Thus, Fe₃O₄@PDA-magnetized MSC therapy offers a promising strategy for optimizing MSC distribution and therapeutic molecule expression in PF treatment, paving the way for broader MSC-based applications.