Co-delivery of retinoic acid and miRNA by functional Au nanoparticles for improved survival and CT imaging tracking of MSCs in pulmonary fibrosis therapy

Abstract

Mesenchymal stem cells (MSCs) have emerged as promising candidates for idiopathic pulmonary fibrosis (IPF) therapy. Increasing the MSC survival rate and deepening the understanding of the behavior of transplanted MSCs are of great significance for improving the efficacy of MSC-based IPF treatment. Therefore, dual-functional Au-based nanoparticles (Au@PEG@PEI@TAT NPs, AuPPT) were fabricated by sequential modification of cationic polymer polyetherimide (PEI), polyethylene glycol (PEG), and transactivator of transcription (TAT) penetration peptide on AuNPs, to co-deliver retinoic acid (RA) and microRNA (miRNA) for simultaneously enhancing MSC survive and real-time imaging tracking of MSCs during IPF treatment. AuPPT NPs, with good drug loading and cellular uptake abilities, could efficiently deliver miRNA and RA to protect MSCs from reactive oxygen species and reduce their expression of apoptosis executive protein Caspase 3, thus prolonging the survival time of MSC after transplantation. In the meantime, the intracellular accumulation of AuPPT NPs enhanced the computed tomography imaging contrast of transplanted MSCs, allowing them to be visually tracked in vivo. This study establishes an Au-based dual-functional platform for drug delivery and cell imaging tracking, which provides a new strategy for MSC-related IPF therapy.