Riboflavin immobilized Fe3O4 magnetic nanoparticles carried with n-butylidenephthalide as targeting-based anticancer agents

Abstract

n-Butylidenephthalide (BP) is a potential anti-cancer drug, which can be extracted from Angelica sinensis (Danggui). Previous reports have shown the effectiveness of BP in treating cancer diseases. However, BP has no targeting capacity towards specific cancer cells. To improve treatment efficiency and reduce the dose of BP used in cancer treatment, targeting-based approaches should be developed. In the present study, we used riboflavin-5'-phosphate (RFMP) immobilized iron oxide magnetic nanoparticles (Fe3O4 MNPs) as carriers for BP to treat cancer cell lines derived from liver, prostate and breast. These model cancer cells overexpress riboflavin receptors on their cell membrane and are also sensitive to BP treatment. Thus, BP-binding free RFMP on MNPs can be used as probes to target these model cells, whereas BP can be readily released on target cancer cells. Cell viability was twofold lower by using Fe3O4@RFMP MNPs immobilized with BP than that achieved by using free-form BP at a similar amount. Moreover, BP-Fe3O4@RFMP MNPs have no apparent harmful effects on non-target cells. In addition, we evaluated the level of cysteine-aspartic acid protease 3 (caspase 3) in the resultant cell lysate obtained after treatment by BP-Fe3O4@RFMP MNPs to demonstrate that apoptosis is mainly involved in the growth inhibition of target cells. [GRAPHICS] .