Anti-cancer and anti-immunomodulatory properties of novel Arteether in Folic acid-Chitosan-Fe3O4 composite nanoparticle for treatment of breast cancer

Goal: The potent anti-cancer activity of Arteether (ARE) has been the focus of many studies. However, the hydrophobic property of this drug limits its application. To increase the bioavailability of ARE, we formulated a nanosystem (NS) of folic acid (FA), chitosan (CS) and Fe3O4 for delivery of ARE against breast cancer. Material and Methods: The CS coated Fe3O4 was synthesized by co-precipitation of Fe2+ and Fe3+ in CS gel-like solution and next it was conjugated with folic acid (FA) and then ARE. The properties of ARE loaded nanoparticles (NPs) were characterized by dynamic light scattering (DLS), fourier transform-infrared (FTIR) spectra, scanning electron microscopy (SEM), drug loading efficiency and drug release. The bioactivity of this complex was evaluated in vitro and in vivo settings. Tumor volume was measured and the cytokines of IFN-γ and IL-4 were assessed in splenocytes of mice. Findings: DLS showed an average size of 198 nm and the charge of about -7 mV. FTIR spectra confirmed the formation of ARE loaded NPs and SEM indicated solid dense structure. The drug exhibited loading capacity of 20% and significant release in citrate buffer with pH 5.4 compared with phosphate-buffered saline with pH 7.4. The NS showed significant inhibitory effect on growth of 4T1 cell line and tumor volume. It also augmented IFN-γ and IL-4 production in breast cancer bearing mice. ARE in FA-CS- Fe3O4 composite NPs may significantly suppress tumor growth. Conclusion: This NS can be utilized in the nano-drug delivery system for treatment of breast cancer.