Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea.
Macromol Biosci. 2018 Dec;18(12):e1800301. doi: 10.1002/mabi.201800301. Epub 2018 Nov 8.
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.
外泌体 (EXO) 被认为是生物分子的多功能载体；然而，使用 EXO 传递治疗性肽存在一些挑战。在这项研究中，确定了血清来源的 EXO 将酪氨酸酶相关蛋白 2 (TRP2) 肽递送到淋巴结的效率。TRP2 肽成功地整合到 EXO 中，其显示出约 45nm 的均匀且窄的粒径分布。含有 TRP2 的外泌体 (EXO-TRP2) 被有效地内吞到巨噬细胞和树突状细胞中，并呈现点状分布。与 MPLA 一起负载 TRP2 的 EXO (EXO-MPLA-TRP2) 导致 RAW264.7 和 DC2.4 细胞中促炎细胞因子 (TNF-α 和 IL-6) 的强烈释放。最后，荧光标记的 EXO-TRP2 的皮下注射，然后使用体内成像系统 (IVIS) 进行离体成像，仅在注射后 1 小时就在淋巴结中显示出强烈的荧光信号，该信号至少维持到注射后 4 小时。总之，这些发现表明，血清来源的 EXO 可以作为有前途的载体，将治疗性肽递送到淋巴结进行免疫治疗。
