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

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.

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.

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.