Targeted Graphene Oxide Networks: Cytotoxicity and Synergy with Anticancer Agents

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Abstract
An effective strategy to inhibit endocytosis in cancer cells is presented where modified net-type graphene oxide (GO) sheets, bound with multiple cell surface receptors, are introduced and synthesised as novel anti-cancer agents. The results suggest that the binding connects GO sheets with neighbouring lipid rafts, neutralises endocytosis, and causes metabolic deprivation. As a result, tumour cell survival and proliferation are reduced. Live cell confocal microscopy imaging reveals that GO-PEGFA (folate-PEGylated GO) is internalised by tumour cells, while GO-PEGRGD (tripeptide Arg-Gly-Asp PEGylated GO) associates with the external cell membrane (not internalized). In vitro exposure of tumor cells to GO-PEGFA or GO-PEGRGD reduces the cell viability by 35%, compared to 50% reduction using methotrexate (100 µM). The combination of modified GO sheets with methotrexate (MTX) or doxorubicin (DOX) shows a greater toxicity (80% reduction in cell viability) than the individual agents. The proposed setup demonstrates a significant synergy in limiting tumour cell growth.
Funding Information
  • University of Isfahan
  • University of Melbourne

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