Methotrexate loaded on magnetite iron nanoparticles coated with chitosan: Biosynthesis, characterization, and impact on human breast cancer MCF-7 cell line

Abstract

Methotrexate (MTX) is effective therapeutic agent treated many tumors and autoimmune diseases. The aim of our study was to design an effective delivery nanocarrier for methotrexate to improve stability and biodistribution, reduce adverse effects and maximize clinical efficacy. Magnetite nanoparticles (Fe₃O₄-NPs) were synthesized using Pterocladiella. The size of Fe₃O₄-NPs, CS-Fe₃O₄-NPs and MTX/CS-Fe₃O₄-NPs were 37.6, 61.4 and 150 nm respectively. Methotrexate loading efficiency was 74.15% of total amount of MTX loaded on CS-Fe₃O₄-NPs and 39.8% of the loaded drug was initially released and the remaining amount was released through 120 h. The IC₅₀ of MTX and MTX/CS-Fe₃O₄-NPs was 51.4 and 9.7 μg/ml respectively after 72 h. MTX/CS-Fe₃O₄-NPs caused remarkable damage to the membrane of MCF-7 cells led to increasing the LDH activity 5 fold in MCF-7 cells as compared with MTX treated once. DNA fragmentation and caspase-3 activity were higher in MCF-7 cells treated with MTX/CS-Fe₃O₄-NPs than that of MTX. Up-regulation of caspase3 and DHFR genes expression was observed in the treatment with MTX/CS-Fe₃O₄-NPs. The loading of MTX on chitosan coated Fe₃O₄-NPs improves the release and anticancer efficacy of MTX for effective cancer treatment.

Keywords: Anticancer efficacy; MTX; Magnetite nanoparticles.