Search

How graphene oxide (GO) derivatives might affect the cell cycle has been rarely studied. Herein, a GO derivative was fabricated by functionalization of GO with polyethylene glycol (PEG) and polyethylenimine (PEI), and its cytotoxic mechanism was investigated in-depth. It was found that our obtained GO-PEG-PEI nanosheets, not the cytotoxic coating polymer PEI, could induce defect in S phase of the mammalian cell cycle, resulting in decreased DNA synthesis, S phase arrest, and abnormal cytoskeleton structure. Further analysis demonstrated that this damaging effect on S phase could be detected in all five tested mammalian cell lines. Even at seemingly safe concentration (∼90% cells viable), GO-PEG-PEI could still induce S phase defect. Detailed investigations revealed that GO-PEG-PEI could cause genomic DNA damage, activating the intra-S-phase checkpoint control via both the ATM and the ATR signaling pathways. Our work unveils the signaling pathways involved in the interaction of GO-PEG-PEI with mammalian cells, and highlights the necessity and importance of comprehensive investigations of the effects of nanomaterials on cellular pathways, such as the cell cycle in this case, even for those with seemingly little/low cytotoxicity during preliminary evaluations. Our work also highlights the critical roles of surface chemistry in biological effects of nanomaterials. [ABSTRACT FROM AUTHOR]

Efficient and safe gene transfection carriers, especially for hard-to-transfect cells, are urgently demanded in basic biological research and gene therapy applications. Many insect cell lines widely used in molecular cell biology exhibit relatively low transfection efficiencies when treated by conventional non-viral agents. Herein, we develop a novel gene delivery vector by coating graphene oxide (GO) with both polyethylene glycol (PEG) and polyethylenimine (PEI), obtaining a dual-polymer-functionalized nanoscale GO (nGO-PEG-PEI) to transfect insect cells. While exhibiting remarkably reduced cytotoxicity compared with PEI, nGO-PEG-PEI, when used as the plasmid DNA transfection agent to treat Drosophila S2 cells, offers ≈7-fold and ≈2.5-fold higher efficiency compared with those achieved by using bare PEI and Lipofectamine 2000, a widely used commercial transfection agent, respectively. Interestingly, the advantages of nGO-PEG-PEI are even more dramatic when transfecting cells with lower-quality linearized DNA. It is revealed that nGO-PEG-PEI/pDNA complexes enter insect cells via a unique pathway working even at a low temperature, rather different from their entry into mammalian adherent cells. Our results encourage the development of nano-GO-based gene carriers to treat special types of hard-to-transfect cells (e.g., insect cells), and indicate that nanomaterials would enter cells by cell-type-dependent mechanisms, which merit significantly more future attentions. [ABSTRACT FROM AUTHOR]