Document Type : Original
Institute of Polymeric Materials, Faculty of Polymer Engineering, Sahand University of Technology, Tabriz, Iran.
Background and objective: Graphene oxide has been extensively used in theranostics due to its drastic properties, biocompatibility, and chemical stability. Graphene has a large surface area and provides enough space for loading of anticancer drugs. In our study, a novel thermo-and pH-responsive graphene-containing nanocomposite was synthesized for methotrexate (MTX) delivery into cancer cells.
Materials and methods: Triblock copolymer of poly[(2-hydroxyethylmethacrylate)-b-(N-isopropylacrylamide)-b-(dimethylaminoethyl methacrylate)] abbreviated as poly(HEMA-b-NIPAM-b-DMAEMA) was prepared by reversible addition fragmentation chain-transfer (RAFT) polymerization. The triblock copolymer was attached onto the surface of graphene oxide nanoparticles via carboxylic groups of graphene oxide. Structure of poly(HEMA-b-NIPAM-b-DMAEMA) was studied by Fourier transform infrared (FT-IR) spectroscopy and Proton nuclear magnetic resonance (1HNMR). Morphology of the nanocomposite was studied by field emission scanning electron microscope (FESEM) and its thermo-responsive behavior was investigated by lower critical solution temperature (LCST), dynamic light scattering (DLS), and thermogravimetric analysis (TGA). Polydispersity index (PDI) was evaluated by gel permeation chromatography. pH-responsive behavior of the nanocomposite was also studied by evaluation of MTX release from the structure at pH 5.4 and 7.4 in the laboratory.
Results and conclusion: Graphene oxide/poly(HEMA-b-NIPAM-b-DMAEMA) has a sheet-like structure with average thickness of 55.6 nm. The triblock chains successfully covered graphene oxide. Characterization of poly(HEMA-b-NIPAM-b-DMAEMA) resulted in Mn = 26875 g, MW = 33862 g, and PDI = 1.26. Encapsulation efficiency of the structure was 91% for MTX. Release rate of MTX from the graphene nanocomposite was pH-dependent. In a buffer solution, release rate of 31.2% was achieved at pH 7.4 and temperature of 37 °C after 150 h. In comparison, release rate of 52.4% was calculated for pH 5.4 after 150 h at the same temperature. Therefore, the synthesized graphene nanocomposite is an appropriate candidate as a carrier of anticancer drugs in treatment of cancer cells.