One-step reduction and PEIylation of PEGylated nanographene oxide for highly efficient chemo-photothermal therapy

Graphene oxide (GO) has great potential in biomedical applications due to its excellent photothermal effect and drug loading. Herein, dual-functionalized reduced nano-GO (nrGO–PEG/PEI) has been developed as a synergistic system of drug delivery and an NIR-light-absorbing agent. Covalently PEGylated nanographene oxide (nGO–PEG) was simultaneously reduced and PEIylated by bathing with polyethylenimine (PEI 1.8 kDa) solution in water at 80 °C for 2 h to obtain nrGO–PEG/PEI. nrGO–PEG/PEI exhibited low cytotoxicity and excellent dispersibility in physiological environments. Furthermore, nrGO–PEG/PEI had ∼20-fold increment in NIR absorption at 808 nm and ∼2.7-fold increment in doxorubicin (DOX) loading over unreduced nGO–PEG. Loaded DOX could be efficiently released from nrGO–PEG/PEI/DOX in an acidic environment (pH 5.0) and by NIR irradiation. In addition, nrGO–PEG/PEI could be rapidly encapsulated into cells and targeted to the nucleus region. In vitro and in vivo studies demonstrated the remarkable anticancer effects of nrGO–PEG/PEI/DOX with NIR laser irradiation. These results suggest that nrGO–PEG/PEI may be a novel drug delivery platform for controlling chemo-photothermal synergistic cancer therapy.