In Vitro and in Vivo Effects of Graphene Oxide and Reduced Graphene Oxide on Glioblastoma

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2015 Mar 12

PMID 25759581

Citations 63

Authors

Slawomir Jaworski

Ewa Sawosz

Marta Kutwin

Mateusz Wierzbicki

Mateusz Hinzmann

Marta Grodzik

Anna Winnicka

Ludwika Lipinska

Karolina Wlodyga

Andre Chwalibog

Affiliations

Soon will be listed here.

Abstract

Graphene and its related counterparts are considered the future of advanced nanomaterials owing to their exemplary properties. However, information about their toxicity and biocompatibility is limited. The objective of this study is to evaluate the toxicity of graphene oxide (GO) and reduced graphene oxide (rGO) platelets, using U87 and U118 glioma cell lines for an in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane for an in vivo model. The in vitro investigation consisted of structural analysis of GO and rGO platelets using transmission electron microscopy, evaluation of cell morphology and ultrastructure, assessment of cell viability by XTT assay, and investigation of cell proliferation by BrdU assay. Toxicity in U87 glioma tumors was evaluated by calculation of weight and volume of tumors and analyses of ultrastructure, histology, and protein expression. The in vitro results indicate that GO and rGO enter glioma cells and have different cytotoxicity. Both types of platelets reduced cell viability and proliferation with increasing doses, but rGO was more toxic than GO. The mass and volume of tumors were reduced in vivo after injection of GO and rGO. Moreover, the level of apoptotic markers increased in rGO-treated tumors. We show that rGO induces cell death mostly through apoptosis, indicating the potential applicability of graphene in cancer therapy.

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References

Chwalibog A, Sawosz E, Hotowy A, Szeliga J, Mitura S, Mitura K . Visualization of interaction between inorganic nanoparticles and bacteria or fungi. Int J Nanomedicine. 2011; 5:1085-94. PMC: 3023237. DOI: 10.2147/IJN.S13532. View

Grodzik M, Sawosz E, Wierzbicki M, Orlowski P, Hotowy A, Niemiec T . Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo. Int J Nanomedicine. 2011; 6:3041-8. PMC: 3230570. DOI: 10.2147/IJN.S25528. View

Guo X, Mei N . Assessment of the toxic potential of graphene family nanomaterials. J Food Drug Anal. 2014; 22(1):105-115. PMC: 6350507. DOI: 10.1016/j.jfda.2014.01.009. View

Shan C, Yang H, Han D, Zhang Q, Ivaska A, Niu L . Water-soluble graphene covalently functionalized by biocompatible poly-L-lysine. Langmuir. 2009; 25(20):12030-3. DOI: 10.1021/la903265p. View

Zhu M, Weiss R . Increased common fragile site expression, cell proliferation defects, and apoptosis following conditional inactivation of mouse Hus1 in primary cultured cells. Mol Biol Cell. 2007; 18(3):1044-55. PMC: 1805091. DOI: 10.1091/mbc.e06-10-0957. View

Liao K, Lin Y, Macosko C, Haynes C . Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater Interfaces. 2011; 3(7):2607-15. DOI: 10.1021/am200428v. View

Cohen-Tanugi D, Grossman J . Water desalination across nanoporous graphene. Nano Lett. 2012; 12(7):3602-8. DOI: 10.1021/nl3012853. View

Liu Z, Robinson J, Sun X, Dai H . PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc. 2008; 130(33):10876-7. PMC: 2597374. DOI: 10.1021/ja803688x. View

Shakur S, Bit-Ivan E, Watkin W, Merrell R, Farhat H . Multifocal and multicentric glioblastoma with leptomeningeal gliomatosis: a case report and review of the literature. Case Rep Med. 2014; 2013:132679. PMC: 3870073. DOI: 10.1155/2013/132679. View

10.

Ribatti D, Vacca A, Roncali L, Dammacco F . The chick embryo chorioallantoic membrane as a model for in vivo research on anti-angiogenesis. Curr Pharm Biotechnol. 2001; 1(1):73-82. DOI: 10.2174/1389201003379040. View

11.

Jaworski S, Sawosz E, Grodzik M, Winnicka A, Prasek M, Wierzbicki M . In vitro evaluation of the effects of graphene platelets on glioblastoma multiforme cells. Int J Nanomedicine. 2013; 8:413-20. PMC: 3559082. DOI: 10.2147/IJN.S39456. View

12.

Tabunoki H, Saito N, Suwanborirux K, Charupant K, Satoh J . Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids. Cancer Cell Int. 2012; 12(1):14. PMC: 3441782. DOI: 10.1186/1475-2867-12-14. View

13.

Yang Y, Rigdon W, Huang X, Li X . Enhancing graphene reinforcing potential in composites by hydrogen passivation induced dispersion. Sci Rep. 2013; 3:2086. PMC: 3694288. DOI: 10.1038/srep02086. View

14.

Sun X, Liu Z, Welsher K, Robinson J, Goodwin A, Zaric S . Nano-Graphene Oxide for Cellular Imaging and Drug Delivery. Nano Res. 2010; 1(3):203-212. PMC: 2834318. DOI: 10.1007/s12274-008-8021-8. View

15.

Zhang J, Zhang F, Yang H, Huang X, Liu H, Zhang J . Graphene oxide as a matrix for enzyme immobilization. Langmuir. 2010; 26(9):6083-5. DOI: 10.1021/la904014z. View

16.

Stockmann-Juvala H, Naarala J, Loikkanen J, Vahakangas K, Savolainen K . Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines. Toxicology. 2006; 225(2-3):234-41. DOI: 10.1016/j.tox.2006.06.006. View

17.

Yang W, Ratinac K, Ringer S, Thordarson P, Gooding J, Braet F . Carbon nanomaterials in biosensors: should you use nanotubes or graphene?. Angew Chem Int Ed Engl. 2010; 49(12):2114-38. DOI: 10.1002/anie.200903463. View

18.

Xu Y, Bai H, Lu G, Li C, Shi G . Flexible graphene films via the filtration of water-soluble noncovalent functionalized graphene sheets. J Am Chem Soc. 2008; 130(18):5856-7. DOI: 10.1021/ja800745y. View

19.

Bernardi A, Frozza R, Hoppe J, Salbego C, Pohlmann A, Battastini A . The antiproliferative effect of indomethacin-loaded lipid-core nanocapsules in glioma cells is mediated by cell cycle regulation, differentiation, and the inhibition of survival pathways. Int J Nanomedicine. 2013; 8:711-28. PMC: 3578504. DOI: 10.2147/IJN.S40284. View

20.

Shih C, Lin S, Sharma R, Strano M, Blankschtein D . Understanding the pH-dependent behavior of graphene oxide aqueous solutions: a comparative experimental and molecular dynamics simulation study. Langmuir. 2011; 28(1):235-41. DOI: 10.1021/la203607w. View