Functionalized graphene oxide against U251 glioma cells and its molecular mechanism.

Graphene and its derivatives with exceptional properties are being exploited for drug delivery and even combined therapies for enhanced antitumor activity and reduced side effects. However, the unfavorable surface chemistry of pristine graphene and reduced graphene oxide made them take covalent and non-covalent functionalization strategies to improve their biocompatibility. Although graphene oxide (GO) is soluble in water owing to its oxygen-containing groups such as carboxylic acid and hydroxyl groups, it is highly accepted when to be modified to improve its colloidal stability in physiological buffers in the presence of salts. In this work, we functionalized GO with Pluronic F127 molecules via non-covalent interaction and found that GO and PF127/GO nanohybrid with a concentration lower than 5 μg/ml have no obvious toxic effect on human astrocytes (AS) and human glioma (U251) cells. Anti-tumor drug doxorubicin (DOX) being loaded onto the PF127/GO nanocarriers by π-π stacking exhibited a high loading capacity of 0.83 mg/mg and loading efficiency of 83%. Our study confirmed that the PF127/GO/DOX (PGD) induced a higher apoptosis rate (12.27 ± 0.06%) of U251 cells than that of free DOX (8.20 ± 0.06%) (P < 0.05). Western blotting results indicated that PGD affected the MAPK signaling pathway and induced the intrinsic pathway of apoptosis for the activation of Caspase-3 in U251 cells, which may provide more evidence for the signal pathway of tumor-targeting therapy.