One-step reduction and PEGylation of graphene oxide for photothermally controlled drug delivery

Here, we developed one-step green reduction and PEGylation of nanosized graphene oxide (NGO) to obtain NrGO/PEG as a photothermally controllable drug delivery system. NrGO/PEG was synthesized by bathing methoxypolyethylene glycol amine (mPEG-NH₂) and NGO at 90 °C for 24 h. The NrGO/PEG kept water stability for at least two months, and had ∼14-fold increment in near-infrared (NIR) absorbance and ∼2-fold increment in resveratrol (RV) loading over the unreduced NGO/PEG via π–π and hydrophobic interactions. Exposure of 4T1 cells to NrGO/PEG for 2 h showed 53.6% uptake ratio, and localization of NrGO/PEG in lysosomes instead of mitochondria. NIR irradiation (808 nm laser at 0.6 W/cm²) for 3 min potently enhanced RV release from NrGO/PEG-RV and the cytotoxicity of NrGO/PEG-RV against 4T1 cells, including decrease of cell viability, loss of mitochondrial membrane potential (ΔΨm) and cell apoptosis. Finally, NIR irradiation dramatically enhanced the efficacy of NrGO/PEG-RV in suppressing tumor growth in animal tumor models, further proving the remarkable synergistic action between photothermal effect of NrGO/PEG and RV loaded on NrGO/PEG.