Dendritic cell-derived exosome-entrapped fluorouracil can enhance its anti-colon cancer effect

• Published in: Journal of B.U.ON. : official journal of the Balkan Union of Oncology Vol. 25; no. 3; p. 1413
• Main Authors: Xu, Man, Chen, Qian, Li, Juan, Peng, Li, Ding, Ling
• Format: Journal Article
• Language: English
• Published: Greece 01.05.2020
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Colonic Neoplasms - drug therapy; Dendritic Cells - cytology; Disease Models, Animal; Exosomes - physiology; Fluorouracil - pharmacology; Mice; Mice, Inbred BALB C
• ISSN: 2241-6293

To explore the effectiveness of fluorouracil (FU) entrapped in dendritic cell (DC)-secreted exosomes (DC-Exos) for enhancing its anti-colon cancer effect. DC-Exos were extracted through ultrahigh-speed centrifugation, and the FU-DC-Exos system was constructed using electroporation. Moreover, the influence of FU-DC-Exos on the viability of mouse colon cancer CT26 cells was determined in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining, and pharmacodynamic evaluation was performed in vivo through TUNEL and hematoxylin-eosin (H&E) staining, with the CT26 tumor-bearing mouse model as the study object. Compared with the control group, FU and DC-Exos groups exhibited a lowered proliferation rate of mouse CT26 colon cancer cells, whereas the apoptosis rate of cells in FU-DC-Exos group differed significantly from FU group. According to the wound healing assay, the migration rate of CT26 cells was reduced in FU and DC-Exos groups, and it was evidently different between FU-DC-Exos group and FU group. Moreover, in vivo experiments revealed that DC-Exos alone exhibited a trend of suppressing tumor growth, and that DC-Exos as carriers not only killed tumor cells alone, but also enhanced the anti-colon cancer effect of FU after entrapment. Exos extracted via ultrahigh-speed centrifugation can be used for the preparation of the drug delivery system of FU-DC-Exos via electroporation, and drug-loaded Exos are able to effectively inhibit the proliferation of tumor cells and induce their apoptosis, exerting an anti-tumor effect.