Immunoregulatory Properties of Arteether in Folic Acid-Chitosan-Fe3O4 Composite Nanoparticle in 4T1 Cell Line and Mice Bearing Breast Cancer

Abstract

Background: Many studies have focused on the potent anti-cancer activity of Arteether (ARE). 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 into breast cancer. Materials and Methods: The CS-coated Fe3O4 was synthesized by co-precipitation of Fe2+ and Fe3+ in CS gel-like solution. Then, it was conjugated with FA and 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 Interferon-gamma IFN-γ and interleukin 4 (IL-4) were assessed in mice splenocytes. Results: DLS showed an average size of 198nm and the charge of about -7mV. FTIR confirmed the formation of ARE loaded NPs and SEM indicated its solid, dense structure. The drug exhibited a 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 the 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-based drug delivery system for the treatment of breast cancer.