Chitosan nanoparticle mediated upregulation of microRNA34a expression to suppress the proliferation, migration, invasion of MDA-MB-231 cells

MicroRNA34a is a tumor suppressor microRNA which is significantly down-regulated in breast cancer cells such as MDA-MB-231 cell and has been reported to be used as a therapeutic target for breast cancer. However, the delivery of miRNAs has always been limited by many barriers. In the present study, a miR-34a-loaded gene delivery system based on Chitosan (CS) was prepared in order to deliver exogenous miR-34a into MDA-MB-231 cells and up regulate its expression. At an optimum N/P ratio of (20:1), the particle size, polydispersity index, and ζ potential of CS/miR-34a nanoparticles (NPs) was ~135 nm, 0.30, +34 mV, respectively. Cell uptake experiment and RT-PCR results proved that CS/miR-34a NPs could be taken up by MDA-MB-231 cells and the relative expression level of miR-34a was up regulated. Chitosan alone showed no obvious cytotoxicity towards normal cells like HUVECs, while CS/miR-34a NPs could inhibit the growth of MDA-MB-231 cells. Cell migration, invasion assays indicated that CS/miR-34a NPs can inhibit the migration and invasion of MDA-MB-231 cells. In conclusion, CS can be used as a transfection vector for miR-34a and transport miR-34a into MDA-MB-231 cells to cause up-regulation of miR-34a expression, ultimately exerting biological effects such as inhibiting the proliferation, migration, invasion of MDA-MB-231 cells.