Enhanced Suppression of Disulfide Cross-Linking Micelles Nanocarriers Loaded miR-145 Delivering System via Down-Regulation of MYC and FSCN1 in Colon Cancer Cells.

Colorectal carcinoma is a complex disease accounting for adenoma tumors and an aggressive phenotype, and the third leading cause of cancer death. In the past decades, miRNAs have been associated with molecular pathways of cancer and other diseases. The dysregulated miRNAs play an inhibitory or promoting role in tumorigenesis. Therefore, restoration of tumor-suppressed microRNAs (miRNA) may offer novel therapeutic approaches for cancer treatment. Nevertheless, the poor bioavailability of miRNA due to their rapid enzymatic degradation is a critical barrier in cancer gene therapy. To overcome this dilemma, we designed disulfide cross-linking micelles (DCM) nanocarrier for delivery of miR-145 to colon cancer cells and investigated its therapeutic efficacy in vitro and in vivo. Results indicated that the presence of DCM nanocarrier loaded with miR-145 enhanced selective delivery of miR-145 and facilitated cellular uptake, significantly up-regulating miR-145 expression in HCT-116 cell lines. Consequently, the cell proliferation was inhibited by arresting cell cycle at the G1 phase. Further, apoptosis of HCT-116 cells treated with miR-145 complex nanoparticles may be via downregulation of oncogenes MYC and FSCN1, predicting regulatory targets for miR-145. These results pave the way for further investigations into the potential of miR-145 complex nanocarrier for cancer gene therapy.