Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells. (3rd June 2018)

• Record Type: Journal Article
• Authors: Nosrati, Hamed; Salehiabar, Marziyeh; Davaran, Soodabeh; Danafar, Hossein; Manjili, Hamidreza Kheiri
• Is Part Of: Drug development and industrial pharmacy. Volume 44:Number 6(2018)
• Page Start: 886
• Page End: 894
• Publication Date: 2018-06-03
• Subjects: Drug conjugated -- iron oxide -- magnetic nanoparticles -- L-lysine -- drug delivery -- methotrexate; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2017.1417422
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase enzyme, is a chemotherapeutic agent for treating a diversity of neoplasms. In this study, we design and developed a new formulation of MTX that serves as drug carrier and examined its cytotoxic effect in vitro . This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. The iron oxide magnetic nanoparticles (IONPs) were first surface-coated with L-lysine and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the IONPs surface. MTX-conjugated L-lysine coated IONPs (F-Lys-MTX NPs) was characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The cytotoxicity of the void of MTX and F-Lys-MTX NPs were compared to each other by MTT assay of the treated MCF-7 cell lines. The results showed that the ζ-potential of F-Lys-MTX NPs was about −5.49 mV and the average size was 43.72 ± 4.73 nm. Model studies exhibited the release of MTX via peptide bond cleavage in the presence of proteinase K and at low pH. These studies specify that F-Lys-MTX NPs have a very remarkable anticancer effect, for breast cancer cell lines.