Metabolomic response of osteosarcoma cells to nanographene oxide-mediated hyperthermia


Nanographene oxide (nGO)-mediated hyperthermia has been increasingly investigated as a localized, minimally invasive anticancer therapeutic approach. Near InfraRed (NIR) light irradiation for inducing hyperthermia is particularly attractive, because biological systems mostly lack chromophores that absorb in this spectral window, facilitating the selective heating and destruction of cells which have internalized the NIR absorbing-nanomaterials. However, little is known about biological effects accompanying nGO-mediated hyperthermia at cellular and molecular levels. In this work, well-characterized pegylated nGO sheets with a hydrodynamic size of 300 nm were incubated with human Saos-2 osteosarcoma cells for 24 h and their internalization verified by flow cytometry and confocal microscopy. No effect on cell viability was observed after nGO uptake by Saos-2 cells. However, a proliferation delay was observed due to the presence of nGO sheets in the cytoplasm. H-1 NMR metabolomics was employed to screen for changes in the metabolic profile of cells, as this could help to improve understanding of cellular responses to nanomaterials and provide new endpoint markers of effect. Cells internalizing nGO sheets showed noticeable changes in several metabolites compared to control cells, including decreased levels of several amino acids, taurine and creatine and increased levels of phosphocholine and uridine/adenosine nucleotides. After NIR irradiation, cells showed decreases in glutamate and uridine nucleotides, together with increases in glycerophosphocholine and adenosine monophosphate. Overall, this study has shown that the cellular metabolome sensitively responded to nGO exposure and nGO-mediated hyperthermia and that NMR metabolomics is a powerful tool to investigate treatment responses.




Materials Science


Cicuendez, M; Flores, J; Oliveira, H; Portoles, MT; Vallet-Regi, M; Vila, M; Duarte, IF

nossos autores


This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. M.C. acknowledges the FCT financial support [Post-Doctoral Grant SFRH/BPD/101468/2014] and Operational Program Human Capital (POCH), European Union. H.O. acknowledges financial support FCT SFRH/BPD/111736/2015. M.T.P. acknowledges funding from Ministerio de Economia y Competitividad (projects MAT2013-43299-R and MAT2016-75611-R AEI/FEDER, UE). M.V.R. acknowledges funding from the European Research Council (Advanced Grant VERDI; ERC-2015-AdG Proposal No. 694160). I.F.D. acknowledges the FCT/MCTES for a research contract under the Program "Investigador FCT" 2014. The authors further acknowledge the financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No 739572 - The Discoveries CTR. The Portuguese National NMR Network supported with FCT funds and Bruker BioSpin GmbH for database access are also acknowledged. Thanks also to the staff of the Centro de Citometria y Microscopia de Fluorescencia of the Universidad Complutense de Madrid (Spain) and ICTS Centro Nacional de Microscopia Electronica (Spain) for the assistance in confocal microscopy and AFM studies, respectively.

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