A novel nanocomposite containing graphene oxide and ABC triblock copolymer for methotrexate delivery

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[(۲-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 (۱HNMR). 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 ۵.۴ and ۷.۴ in the laboratory.Results and conclusion: Graphene oxide/poly(HEMA-b-NIPAM-b-DMAEMA) has a sheet-like structure with average  thickness of ۵۵.۶ nm. The triblock chains successfully covered graphene oxide. Characterization of poly(HEMA-b-NIPAM-b-DMAEMA) resulted in Mn = ۲۶۸۷۵ g,  MW = ۳۳۸۶۲ g, and PDI = ۱.۲۶. Encapsulation efficiency of the structure was ۹۱% for MTX. Release rate of MTX from the graphene nanocomposite was pH-dependent. In a buffer solution, release rate of ۳۱.۲% was achieved at pH ۷.۴ and temperature of ۳۷ °C after ۱۵۰ h. In comparison, release rate of ۵۲.۴% was calculated for pH ۵.۴ after ۱۵۰ 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.

Keywords:

Cancer therapy , graphene nanocomposite , methotrexate , pH-responsive , thermo-responsive