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A biocompatible complex has been prepared as gene carrier via electrostatic interaction, which is composed of a polycation, that is, poly[(dimethylamino)ethyl methacrylate] end-capped with cholesterol moiety (Chol-PDMAEMA30), along with a polyanion named poly(aspartic acid)-grafted-poly(ethylene glycol) (PASP-g-PEG). The complexes have less cytotoxicity compared to the case of alone Chol-PDMAEMA30 or branched polyethylenimine (PEI) system. In the present study, biocompatible complexes have been prepared as gene carrier via electrostatic interaction, which is composed of a polycation, that is, poly[(dimethylamino)ethyl methacrylate] end-capped with cholesterol moiety (Chol-PDMAEMA30), along with a polyanion named poly(aspartic acid)-grafted-poly(ethylene glycol) (PASP-g-PEG). We first synthesized polysuccinimide (PSI) via condensation polymerization of aspartic acid, and then used PEG-NH2 to react with the partial pentacyclic rings of PSI to yield a kind of graft copolymer polysuccinimide-grafted-poly(ethylene glycol) (PSI-g-PEG). After hydrolysis of the residual succinimide units, a new biodegradable and biocompatible graft copolymer PASP-g-PEG was prepared successfully. Chol-PDMAEMA30 was synthesized via oxyanion-initiated polymerization, as reported in our previous literature. We investigated the interactions between every pair among calf thymus DNA, Chol-PDMAEMA30, and PASP-g-PEG by agarose gel retardation assay. The results indicate that the prepared complexes could completely bind DNA and may become more stable during systemic circulation. The complexes have less cytotoxicity compared to the case of alone Chol-PDMAEMA30 or branched polyethylenimine (PEI) system. Furthermore, the physicochemical properties of the complexes were also investigated by zeta potential, transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. These biodegradable and biocompatible polymeric carriers have potential applications in gene delivery. [ABSTRACT FROM PUBLISHER]

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]