SPECIFIC TARGETING OF FOLATE RECEPTOR BY METHOTREXATE CONJUGATED MODIFIED MAGNETIC NANOPARTICLES: ENZYMATIC RELEASE AND CYTOTOXIC STUDY

摘要

Magnetic nanocarriers have been used for specific drug delivery to release therapeutic drugs into target cancer cells. We used bifunctional methotrexate (MTX) conjugated magnetic nanoparticles (MNPs) (~37 nm) engineered by dopamine–polyethylene glycol to targeted folate receptor (FR)-positive cancer cells. For this purpose, MTX was chemically loaded on to MNPs with N, N-dicyclohexylcarbodiimide (DCC) in the absence of NHS at 0°C. Activation process of MTX was analyzed via synthesis of different MTX methyl esters through HPLC instrument. The HPLC analysis showed that in a selective condition and in the presence of 1.1 equiv. of reactiveagent,a-carboxyl group of MTX was more active. Enzymatic release study of MTX demonstrated that the highest rate of drug release was at pH=3.8 with protease enzyme (85.12%). Also, cytotoxicity assay revealed that Fe₃O₄-DPA-PEG-MTX NPs were able to target over expressed FR cell line (MCF-7) but did not have any effect on FR-negative A549 cells and significantly inhibit them.