Dual-targeting and specific delivery of tamoxifen to cancer cells by modified magnetic nanoparticles using hyaluronic acid and folic acid

Tamoxifen (TMX) which serves as the best clinical option for the treatment of breast cancer may trigger major dose-dependent side effects due to its poor solubility. Therefore, the use of lower TMX doses utilizing nano-enabled drug delivery systems offers multiple benefits to improving drug specified concentration, safety, and long-term release. In this study, we synthesized targeted magnetic nanoparticles (MNPs) containing folic acid (FA) and hyaluronic acid (HA) to improve drug delivery of TMX. After investigations utilizing Fourier-transform infrared spectroscopy and field emission scanning electron microscope, we found that the surface of MNPs was well modified with targeting agents, and the size of the Fe3O4-DPN-HA-FA NPs was determined at ∼153 (±3.3) nm. Furthermore, the release of 81% TMX after 120 h indicated that there was a controlled pattern of drug release from the modified MNPs. Besides that, the MTT assay revealed that the viability of MDA-MB-231 cell lines after 48 h and 72 h of treatment is dependent on the time and concentration of Fe3O4-DPN-HA-FA-TMX NPs. Finally, real-time polymerase chain reaction demonstrated that Fe3O4-DPN-HA-FA-TMX NPs could upregulate the expression of Bak1 genes and downregulated the expression of Bclx genes during 24 h treatment. All data confirmed that the presence of HA and FA on the surface of nanocarriers and the active targeting employing the nanocarriers can be a useful step to obliterate the breast cancer cells.