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Triggering cell death by nanographene oxide mediated hyperthermia

Significance Statement

Our initial studies about pegylated graphene oxide nanosheets (PEG-nGO)  demonstrated that the uptake of PEG-nGO by the cells plays an extremely important role in defining controlled treatments, as they proved that there is an specific uptake timing  as a function of the cell type involved (and its tumoral or healthy nature)  which could be used to increase selectivity on the treatment. Moreover, PEG branching and size effects on cell uptake were also found to play an important role on nanoparticle uptake and toxicity. The  internalization of a nGO decorated with the commonly used high-branched PEG was revealed to be less efficient and more toxic when compared with the PEG linear version. Moreover, we found that after cell internalization, PEG-nGO was localized on F-actin filaments inducing cell-cycle alterations for a commonly used dose on the literature. Since direct or indirect generation of reactive oxygen species (ROS) and oxidative stress induction are the leading toxicity mechanisms proposed for engineered nanomaterials, we focused our efforts on the study and control of the effects of GOn on the intracellular ROS content of bone cancer model cells. Considering both the proliferation delay observed and the enhanced ROS production induced by GOs in the, it was also of interest to analyze the effects of these materials on the cell-cycle phases, and apoptosis. It was observed, that the SubG1 fraction (corresponding to cells with fragmented DNA and indicative of apoptosis) showed a slight but significant apoptosis increase induced by GOn in almost all cell types and some growth delay was observed and revealed an alteration of the capacity for mitotic division. These impacting findings revealed that a safe application of this therapy needed dosage modifications and control in order to avoid cell toxicity.

additional references: Nanotechnology. 23 (2012) 465103; Biomaterials. 2013 (34) 1562-9



Triggering cell death by nanographene oxide mediated hyperthermia- - Global Medical Discovery











Vila M, Matesanz MC, Gonçalves G, Feito MJ, Linares J, Marques PA, Portolés MT, Vallet-Regi M.

Nanotechnology. 2014 Jan 24;25(3):035101.

Department of Inorganic and Bioinorganic Chemistry, Faculty of Pharmacy, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, E-28040-Madrid, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain.


Graphene oxide (GO) has been proposed as an hyperthermia agent for anticancer therapies due to its near-infrared (NIR) optical absorption ability which, with its small two-dimensional size, could have a unique performance when compared to that of any other nanoparticle. Nevertheless, attention should be given to the hyperthermia route and the kind of GO-cell interactions induced in the process. The hyperthermia laser irradiation parameters, such as exposure time and laser power, were investigated to control the temperature rise and consequent damage in the GOs containing cell culture medium. The type of cell damage produced was evaluated as a function of these parameters. The results showed that cell culture temperature (after irradiating cells with internalized GO) increases preferentially with laser power rather than with exposure time. Moreover, when laser power is increased, necrosis is the preferential cell death leading to an increase of cytokine release to the medium.

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