CT/NIRF dual-modal imaging tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with Au nanoparticles in silica-induced pulmonary fibrosis

摘要

Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in cell-based therapies and regenerative medicine. Efficient tracking of MSCs is an urgent clinical need that will help us to understand their behavior after transplantation and allow adjustment of therapeutic strategies. However, no clinically approved tracers are currently available, which limits the clinical translation of stem cell therapy. In this study, a nanoparticle (NP) for computed tomography (CT)/fluorescence dual-modal imaging, Au@Albumin@ICG@PLL (AA@ICG@PLL), was developed to track bone marrow-derived mesenchymal stem cells (BMSCs) that were administered intratracheally into mice with silica-induced pulmonary fibrosis, which facilitated understanding of the therapeutic effect and the possible molecular mechanism of stem cell therapy. The AuNPs were first formed in bovine serum albumin (BSA) solution and modified with indocyanine green (ICG), and subsequently coated with a poly-l-lysine (PLL) layer to enhance intracellular uptake and biocompatibility. BMSCs were labeled with AA@ICG@PLL NPs with high efficiency without an effect on biological function or therapeutic capacity. The injected AA@ICG@PLL-labeled BMSCs could be tracked via CT and near-infrared fluorescence (NIRF) imaging for up to 21 days after transplantation. Using these NPs, the molecular anti-inflammatory mechanism of transplanted BMSCs was revealed, which included the downregulation of proinflammatory cytokines, suppression of macrophage activation, and delay of the fibrosis process. This study suggests a promising role for imaging-guided MSC-based therapy for pulmonary fibrosis, such as idiopathic pulmonary fibrosis (IPF) and pneumoconiosis.