lipid-a and 5-carboxytetramethylrhodamine-succinimidyl-ester

Exosomes (EXO) are considered to be versatile carriers for biomolecules; however, the delivery of therapeutic peptides using EXOs poses several challenges. In this study, the efficiency of serum-derived EXOs in delivering tyrosinase-related protein-2 (TRP2) peptides to lymph nodes is determined. TRP2 peptides are successfully incorporated into EXOs, which show a uniform and narrow size distribution of around 45 nm. The TRP2-incorporated exosomes (EXO-TRP2) are efficiently internalized into macrophages and dendritic cells, and are seen to display a punctate distribution. EXOs loaded with TRP2 together with MPLA, (EXO-MPLA-TRP2) result in a strong release of proinflammatory cytokines (TNF-α and IL-6) from both RAW264.7 and DC2.4 cells. Finally, subcutaneous injection of fluorescently labeled EXO-TRP2 followed by ex vivo imaging using in vivo imaging system (IVIS) show a strong fluorescent signal in the lymph nodes after only 1 h, which is maintained until at least 4 h after injection. Taken together, the findings suggest that serum-derived EXOs can serve as promising carriers to deliver therapeutic peptides to lymph nodes for immunotherapy.

Topics: Adjuvants, Immunologic; Animals; Biological Transport; Cell Line; Dendritic Cells; Drug Compounding; Drug Delivery Systems; Electroporation; Exosomes; Fluorescent Dyes; Gene Expression; Injections, Subcutaneous; Interleukin-6; Lipid A; Lymph Nodes; Membrane Proteins; Mice; Peptide Fragments; RAW 264.7 Cells; Rhodamines; Saponins; Tumor Necrosis Factor-alpha