Delivery of Oridonin and Methotrexate via PEGylated Graphene Oxide.

Graphene oxide (GO) possessing plenty of hydroxyls and carboxyls is often used in the field of biomedicine. To improve its water solubility and biocompatibility, 6-armed poly(ethylene glycol) (PEG) was bonded on the surface of GO sheets via a facile amidation process to form the universal drug delivery platform (GO-PEG10K-6arm) with a 200 nm size in favor of the enhanced permeability and retention effect. Herein, we prepared the stable and biocompatible platform of GO-PEG10K-6arm under mild conditions and characterized the chemical structure and micromorphology via thermogravimetric analysis and atomic force microscopy. This nanosized GO-PEG10K-6arm was found to be of very low toxicity to human normal cells of 293T and tumor cells of CAL27, MG63, and HepG2. Moreover, oridonin and methotrexate (MTX), widely used hydrophobic cancer chemotherapy drugs, were compounded with GO-PEG10K-6arm via π-π stacking and hydrophobic interactions so as to afford nanocomplexes of oridonin@GO-PEG10K-6arm and MTX@GO-PEG10K-6arm, respectively. Both nanocomplexes could quickly enter into tumor cells, which was evidenced by inverted fluorescence microscopy using fluorescein isothiocyanate as a probe, and they both showed remarkably high cytotoxicity to the tumor cells of CAL27, MG63, and HepG2 within a broad range of concentration in comparison with free drugs. This kind of nanoscale drug delivery system based on GO-PEG10K-6arm may have potential applications in biomedicine, and GO-PEG10K-6arm would be a universal and available carrier for extensive hydrophobic anticarcinogens.