The homologous tumor-derived-exosomes loaded with miR-1270 selectively enhanced the suppression effect for colorectal cancer cells.

Abstract

Colorectal cancer (CRC), known as prevalent cancer, has risen to be the leading cause of cancer-related death. Engineered exosomes had attracted much attention since they acted as carriers to deliver small molecule drugs, therapeutic nucleic acids, and polypeptides to treat a series of cancers. Here, we found that the PKH-26 labeled exosomes, which were derived from the CRC cells, could be efficiently absorbed by SW1116 cells and had an abundant fluorescence distribution in tumors, compared with the exosomes derived from mesenchymal stem cells (MSC) and HepG2 cells. This Research demonstrated that engineered CRC-exosomes loaded with functional miR-1270 (Exo-miR-1270) enriched in miR-1270 strongly inhibited the proliferation by CCK-8 and EdU assays, migration by wound-healing and transwell assays, and promoted the apoptosis for CRC cells through flow cytometry. MiR-1270 overexpression delivered by CRC exosomes contributed to inhibiting the tumor growth potential of CRC invivo and increasing the overall survival of the mice. Moreover, the safety evaluation results showed that CRC-exosomes loaded with functional miR-1270-mimics had no toxicity for other organs by histopathological analysis and no influence on the vital chemistry and hematology parameters for mice invivo safety evaluation. These results indicate that Exo-miR-1270 can effectively treat CRC tumors by intravenous administration. Our work provided a foundation that the homologous tumor-derived exosomes mediated miRNA delivery for the treatment of CRC.