Engineered Exosomes Loaded with Triptolide: An Innovative Approach to Enhance Therapeutic Efficacy in Rheumatoid Arthritis

•Development of Engineered Exosomes: The study successfully isolated exosomes from human rheumatoid arthritis fibroblasts (hRAF-Exo) and engineered them by loading with triptolide (TP), creating hRAF-Exo@TP.•Inhibitory Effect on RA Fibroblasts: In cellular experiments, hRAF-Exo@TP demonstrated a significant inhibitory effect on the proliferative activity of human RA fibroblasts, suggesting potential therapeutic benefits.•Selective Targeting in Mouse Model: The study observed remarkable selectivity of hRAF-Exo@TP for lesion sites in a murine collagen-induced arthritis (CIA) model, indicating targeted therapeutic action.•Selective Targeting in Mouse Model: The study observed remarkable selectivity of hRAF-Exo@TP for lesion sites in a murine collagen-induced arthritis (CIA) model, indicating targeted therapeutic action. Exosomes are small, membrane-bound vesicles secreted by cells into the extracellular environment. They play a crucial role in various biological processes, including immune response, cell-to-cell signaling, and tumor progression. Exosomes have attracted attention as potential targets for therapeutic intervention, drug delivery, and biomarker detection. In this study, we aimed to isolate exosomes from human RA fibroblasts (hRAF-Exo) and load them with triptolide (TP) to generate engineered exosomes (hRAF-Exo@TP). Transmission electron microscopy, particle size analysis, and western blotting for protein detection were employed to characterize hRAF-Exo. Furthermore, a murine model of collagen-induced arthritis (CIA) was employed to observe the distinct affinity of hRAF-Exo@TP towards the afflicted area. Cellular experiments demonstrated the inhibitory effect of hRAF-Exo@TP on the proliferative activity of human RA fibroblasts. Additionally, it exhibited remarkable selectivity for lesion sites in a CIA mouse model. Exosomes loaded with TP may enhance the therapeutic effects on RA in mice. Our study provides a promising avenue for the treatment of RA in the future.