Inhibition of miR-96 and miR-183 expression in treatment with fisetin-loaded chitosan nanoparticles in breast cancer cell lines

Several efforts have been made to improve the treatment of breast cancer. Nanotechnology has been proposed as a promising strategy for the formulation of pharmaceutical compounds and increasing their efficiency. Fisetin is a natural flavonoid with anti-cancer properties. This study was conducted with the aim of improving the anti-cancer effect of fisetin with the chitosan nanoparticles delivery system and investigating some molecular pathways after treating breast cancer cell lines (MCF7 and MDA-MB231).  After the synthesis of chitosan nanoparticles, the shape, size and surface charge of nanoparticles were measured by SEM, DLS and zeta sizer. Drug loading in nanoparticles was confirmed by FTIR. The drug release rate was evaluated in acidic and neutral environments.  Also, the cell cytotoxicity of fisetin and nanofisetin was investigated using MTT assay. The expression level of miR-183 and miR-96 investigated in both cell lines using real-time PCR.  Our results showed that fisetin was successfully loaded into nanoparticles. The pH-dependent release of this nanosystem facilitated the release of fisetin in the acidic environment of the tumor. Chitosan nanoparticles containing fisetin with a size of 60 nm with significant efficiency exhibited higher toxicity to the viability of cells than free fisetin, and this decrease in survival was more pronounced for the triple negative MDA-MB-231. Fisetin also significantly decreased the expression of miR-96 and miR-183 in both cell lines.  The nanoformulation of this herbal compound and its effect can present nanofisetin as a potential candidate for the treatment of metastatic breast cancer.