Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

• Published in: Macromolecular bioscience 2018-12, Vol.18 (12), p.e1800301-n/a
• Main Authors: Park, Ok, Choi, Eun Seo, Yu, Gyeonghui, Kim, Jun Yeong, Kang, Yoon Young, Jung, Heesun, Mok, Hyejung
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacokinetics; Animals; Biological Transport; Biomolecules; Cell Line; cytokine; Cytokines; dendritic cell; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Drug Compounding - methods; Drug Delivery Systems - methods; Electroporation - methods; exosome; Exosomes; Exosomes - chemistry; Exosomes - metabolism; Exosomes - transplantation; Fluorescence; Fluorescent Dyes - pharmacokinetics; Gene Expression; Immunotherapy; Inflammation; Injection; Injections, Subcutaneous; Interleukin-6 - genetics; Interleukin-6 - immunology; Lipid A - analogs & derivatives; Lipid A - chemistry; Lipid A - immunology; Lipid A - pharmacokinetics; Load distribution (forces); lymph node; Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymphatic system; Macrophages; Membrane Proteins - chemistry; Membrane Proteins - immunology; Membrane Proteins - pharmacokinetics; Mice; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptide Fragments - pharmacokinetics; Peptides; Proteins; RAW 264.7 Cells; Rhodamines - pharmacokinetics; Saponins - chemistry; Size distribution; Stress concentration; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tyrosinase; tyrosinase‐related protein‐2 peptide
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201800301

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. Tyrosinase related protein‐2 peptide and immune stimulator are incorporated within exosomes, which allow efficient cellular delivery in vitro and lymphatic accumulation in vivo. Thus, the findings suggest that serum‐derived exosomes can serve as promising carriers for immunotherapy using therapeutic peptides.