Abstract

A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for ‘smart’ treatment of cancer by chemo/hyperthermia approach. For this objective, Fe3O4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N,N′-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe3O4@P(DMAEMA-co-MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.

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