Development of an Organ-Directed Exosome-Based siRNA-Carrier Derived from Autologous Serum for Lung Metastases and Testing in the B16/BL6 Spontaneous Lung Metastasis Model.

Exosomes are nano-sized extracellular vesicles that are known to carry various messages to distant cells. It was recently reported that cancer-derived exosomes are orientated to metastatic organs. However, there are no reports on drug carrier development using autologous serum-derived exosomes in vivo. The purpose of this study was to deliver therapeutic siRNAs for melanoma lung metastases using autologous serum-derived exosomes. Primary tumors were induced by subcutaneously injecting melanoma cells into the hindlimbs of female C57BL/6 mice. Primary tumors were surgically removed on day 14. On day 21 after tumor removal, lung metastases were evaluated. Exosomes were isolated from serum collected from mice on days 0, 3, 7, 10, and 14 after primary tumor inoculation. After isolating serum exosomes, siRNA-loaded exosomes were prepared. siRNA-loaded exosomes were intravenously injected into the B16/BL6 spontaneous lung metastasis model mice on days 0, 3, 7, and 10 after tumor removal. siRNA-loaded exosomes prepared with autologous serum-derived exosomes significantly decreased the number of metastatic lung colonies. Autologous serum-derived exosomes, which have high organ accumulation, could potentially be used as efficient carriers of therapeutic siRNAs for melanoma patients with lung metastases.