Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule.
OBJECTIVE
Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells.


METHODS
The successful reduction of graphene oxide (GO) to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO). Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells.


RESULTS
The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3.


CONCLUSIONS
Our data demonstrate a single, simple green approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic compound resveratrol, which has similar efficacy in the reduction of GO to rGO. Resveratrol-based GO reduction would facilitate large-scale production of graphene-based materials for the emerging graphene-based technologies and biomedical applications.
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
Sangiliyandi
S
Gurunathan
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
Jae Woong
JW
Han
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
Eun Su
ES
Kim
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
Jung Hyun
JH
Park
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
Jin-Hoi
JH
Kim
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry*; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D010087:Oxides; D013267:Stilbenes; D006108:Graphite; D000077185:Resveratrol
ROS generation; Raman spectroscopy; UV-vis spectroscopy; membrane integrity; reduced graphene oxide; scanning electron microscopy