Well-defined Graphene Oxide as a Potential Component in Lung Cancer Therapy

Author(s): Agnieszka Zuchowska, Elzbieta Jastrzebska, Marta Mazurkiewicz-Pawlicka, Artur Malolepszy, Leszek Stobinski, Maciej Trzaskowski, Zbigniew Brzozka*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 1 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Graphene oxide (GO) has unique physical and chemical properties that can be used in anticancer therapy - especially as a drug carrier. Graphene oxide, due to the presence of several hybrid layers of carbon atoms (sp2), has a large surface for highly efficient drug loading. In addition, GO with a large number of carboxyl, hydroxyl and epoxy groups on its surface, can charge various drug molecules through covalent bonds, hydrophobic interactions, hydrogen bonds and electrostatic interactions.

Objective: The aim of our work was to evaluate the possibility of future use of graphene oxide as an anticancer drug carrier.

Methods: In this paper, we present GO synthesis and characterization, as well as a study of its biological properties. The cytotoxic effect of well-defined graphene oxide was tested on both carcinoma and non-malignant cells isolated from the same organ, which is not often presented in the literature.

Results: The performed research confirmed that GO in high concentrations (> 300 µgmL-1) selectively decreased the viability of cancer cell line. Additionally, we showed that the GO flakes have a high affinity to cancer cell nucleus which influences their metabolism (inhibition of cancer cell proliferation). Moreover, we have proved that GO in high concentrations can cause cell membrane damage and generate reactive oxygen species on a low level mainly in cancer cells.

Conclusion: The proposed GO could be useful in anticancer therapy. A high concentration of GO selectively causes the death of tumor cells, whereas GO with low concentration could be a potential material for anticancer drug loading.

Keywords: Graphene oxide, lung cancer, cytotoxicity, graphene-based materials, graphene, drug carrier.

[1]
Anand, P.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Tharakan, S.T.; Lai, O.S.; Sung, B.; Aggarwal, B.B. Cancer is a preventable disease that requires major lifestyle changes. Pharm. Res., 2008, 25(9), 2097-2116.
[http://dx.doi.org/10.1007/s11095-008-9661-9] [PMID: 18626751]
[2]
World Cancer Report. World Health Organization, 2014.
[3]
Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer, 2005, 5(3), 161-171.
[http://dx.doi.org/10.1038/nrc1566] [PMID: 15738981]
[4]
Wang, X.; Yang, L.; Chen, Z.G.; Shin, D.M. Application of nanotechnology in cancer therapy and imaging. CA Cancer J. Clin., 2008, 58(2), 97-110.
[http://dx.doi.org/10.3322/CA.2007.0003] [PMID: 18227410]
[5]
Filippousi, M.; Siafaka, P.I.; Amanatiadou, E.P.; Nanaki, S.G.; Neratzaki, M.; Bikiaris, D.N.; Vizirianakis, I.S.; van Tendeloo, G. Modified chitosan coated mesoporous strontium hydroxyapatite nanorods as drug carriers. J. Mater. Chem. B Mater. Biol. Med., 2015, 3, 5991-6000.
[http://dx.doi.org/10.1039/C5TB00827A]
[6]
Pourjavadi, A.; Tehrani, Z.M.; Jokar, S. Functionalized mesoporous silica-coated magnetic graphene oxide by polyglycerol-G-polycaprolactone with pH-responsive behavior: Designed for targeted and controlled doxorubicin delivery. J. Ind. Eng. Chem., 2015, 28, 45-53.
[http://dx.doi.org/10.1016/j.jiec.2015.01.021]
[7]
Kaminski, G.A.T.; Sierakowski, M.R.; Pontarolo, R.; Santos, L.A.; de Freitas, R.A. Layer-by-layer polysaccharide-coated liposomes for sustained delivery of epidermal growth factor. Carbohydr. Polym., 2016, 140, 129-135.
[http://dx.doi.org/10.1016/j.carbpol.2015.12.014] [PMID: 26876836]
[8]
Gokce, E.H.; Korkmaz, E.; Dellera, E.; Sandri, G.; Bonferoni, M.C.; Ozer, O. Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int. J. Nanomedicine, 2012, 7, 1841-1850.
[http://dx.doi.org/10.2147/IJN.S29710] [PMID: 22605933]
[9]
Hami, Z.; Amini, M.; Ghazi-Khansari, M.; Rezayat, S.M.; Gilani, K. Synthesis and in vitro evaluation of a pH-sensitive PLA-PEG-folate based polymeric micelle for controlled delivery of docetaxel. Colloids Surf. B Biointerfaces, 2014, 116, 309-317.
[http://dx.doi.org/10.1016/j.colsurfb.2014.01.015] [PMID: 24503352]
[10]
Stroh, M.; Zimmer, J.P.; Duda, D.G.; Levchenko, T.S.; Cohen, K.S.; Brown, E.B.; Scadden, D.T.; Torchilin, V.P.; Bawendi, M.G.; Fukumura, D.; Jain, R.K. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat. Med., 2005, 11(6), 678-682.
[http://dx.doi.org/10.1038/nm1247] [PMID: 15880117]
[11]
Jeyamohan, P.; Hasumura, T.; Nagaoka, Y.; Yoshida, Y.; Maekawa, T.; Kumar, D.S. Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy. Int. J. Nanomedicine, 2013, 8, 2653-2667.
[PMID: 23926428]
[12]
Yan, L.; Zhao, F.; Li, S.; Hu, Z.; Zhao, Y. Low-toxic and safe nanomaterials by surface-chemical design, carbon nanotubes, fullerenes, metallofullerenes, and graphenes. Nanoscale, 2011, 3(2), 362-382.
[http://dx.doi.org/10.1039/C0NR00647E] [PMID: 21157592]
[13]
Lima-Tenório, M.K.; Pineda, E.A.; Ahmad, N.M.; Fessi, H.; Elaissari, A. Magnetic nanoparticles: In vivo cancer diagnosis and therapy. Int. J. Pharm., 2015, 493(1-2), 313-327.
[http://dx.doi.org/10.1016/j.ijpharm.2015.07.059] [PMID: 26232700]
[14]
Wickline, S.A.; Neubauer, A.M.; Winter, P.M.; Caruthers, S.D.; Lanza, G.M. Molecular imaging and therapy of atherosclerosis with targeted nanoparticles. J. Magn. Reson. Imaging, 2007, 25(4), 667-680.
[http://dx.doi.org/10.1002/jmri.20866] [PMID: 17347992]
[15]
Li, Y.; Dong, H.; Li, Y.; Shi, D. Graphene-based nanovehicles for photodynamic medical therapy. Int. J. Nanomedicine, 2015, 10, 2451-2459.
[PMID: 25848263]
[16]
Yang, K.; Zhang, S.; Zhang, G.; Sun, X.; Lee, S.T.; Liu, Z. Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett., 2010, 10(9), 3318-3323.
[http://dx.doi.org/10.1021/nl100996u] [PMID: 20684528]
[17]
Jung, H.S.; Lee, M.Y.; Kong, W.H.; Do, I.H.; Hahn, S.K. Nano graphene oxide–hyaluronic acid conjugate for target specific cancer drug delivery. RSC Advances, 2014, 4, 14197-14200.
[http://dx.doi.org/10.1039/c4ra00605d]
[18]
Kim, H.; Namgung, R.; Singha, K.; Oh, I.K.; Kim, W.J. Graphene oxide-polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool. Bioconjug. Chem., 2011, 22(12), 2558-2567.
[http://dx.doi.org/10.1021/bc200397j] [PMID: 22034966]
[19]
Priyadarsini, S.; Mohanty, S.; Mukherjee, S.; Basu, S.; Mishra, M. Graphene and graphene oxide as nanomaterials for medicine and biology application. J Nanostruct Chem, 2018, 8, 123-137.
[http://dx.doi.org/10.1007/s40097-018-0265-6]
[20]
Geim, A.K.; Novoselov, K.S. The rise of graphene. Nat. Mater., 2007, 6(3), 183-191.
[http://dx.doi.org/10.1038/nmat1849] [PMID: 17330084]
[21]
Singh, V.; Joung, D.; Zhai, L.; Das, S.; Khondaker, S.I.; Seal, S. Graphene based materials: Past, present and future. Prog. Mater. Sci., 2011, 56, 1178-1271.
[http://dx.doi.org/10.1016/j.pmatsci.2011.03.003]
[22]
Wu, J.; Yang, R.; Zhang, L.; Fan, Z.; Liu, S. Cytotoxicity effect of graphene oxide on human MDA-MB-231 cells. Toxicol. Mech. Methods, 2015, 25(4), 312-319.
[http://dx.doi.org/10.3109/15376516.2015.1031415] [PMID: 25996036]
[23]
Zhang, Y.; Ali, S.F.; Dervishi, E.; Xu, Y.; Li, Z.; Casciano, D.; Biris, A.S. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano, 2010, 4(6), 3181-3186.
[http://dx.doi.org/10.1021/nn1007176] [PMID: 20481456]
[24]
Dreyer, D.R.; Park, S.; Bielawski, C.W.; Ruoff, R.S. The chemistry of graphene oxide. Chem. Soc. Rev., 2010, 39(1), 228-240.
[http://dx.doi.org/10.1039/B917103G] [PMID: 20023850]
[25]
Bengtson, S.; Kling, K.; Madsen, A.M.; Noergaard, A.W.; Jacobsen, N.R.; Clausen, P.A.; Alonso, B.; Pesquera, A.; Zurutuza, A.; Ramos, R.; Okuno, H.; Dijon, J.; Wallin, H.; Vogel, U. No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro. Environ. Mol. Mutagen., 2016, 57(6), 469-482.
[http://dx.doi.org/10.1002/em.22017] [PMID: 27189646]
[26]
Liu, Y.; Wang, X.; Wang, J.; Nie, Y.; Du, H.; Dai, H.; Wang, J.; Wang, M.; Chen, S.; Hei, T.K.; Deng, Z.; Wu, L.; Xu, A. Graphene oxide attenuates the cytotoxicity and mutagenicity of PCB 52 via activation of genuine autophagy. Environ. Sci. Technol., 2016, 50(6), 3154-3164.
[http://dx.doi.org/10.1021/acs.est.5b03895] [PMID: 26876502]
[27]
Liu, Y.; Luo, Y.; Wu, J.; Wang, Y.; Yang, X.; Yang, R.; Wang, B.; Yang, J.; Zhang, N. Graphene oxide can induce in vitro and in vivo mutagenesis. Sci. Rep., 2013, 3, 3469.
[http://dx.doi.org/10.1038/srep03469] [PMID: 24326739]
[28]
Lammel, T.; Boisseaux, P.; Fernández-Cruz, M.L.; Navas, J.M. Internalization and cytotoxicity of graphene oxide and carboxyl graphene nanoplatelets in the human hepatocellular carcinoma cell line Hep G2. Part. Fibre Toxicol., 2013, 10, 27.
[http://dx.doi.org/10.1186/1743-8977-10-27] [PMID: 23849434]
[29]
Chang, Y.; Yang, S.T.; Liu, J.H.; Dong, E.; Wang, Y.; Cao, A.; Liu, Y.; Wang, H. In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol. Lett., 2011, 200(3), 201-210.
[http://dx.doi.org/10.1016/j.toxlet.2010.11.016] [PMID: 21130147]
[30]
Xu, Z.; Wang, S.; Li, Y.; Wang, M.; Shi, P.; Huang, X. Covalent functionalization of graphene oxide with biocompatible poly(ethylene glycol) for delivery of paclitaxel. ACS Appl. Mater. Interfaces, 2014, 6(19), 17268-17276.
[http://dx.doi.org/10.1021/am505308f] [PMID: 25216036]
[31]
Hu, W.; Peng, C.; Lv, M.; Li, X.; Zhang, Y.; Chen, N.; Fan, C.; Huang, Q. Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano, 2011, 5(5), 3693-3700.
[http://dx.doi.org/10.1021/nn200021j] [PMID: 21500856]
[32]
Chen, J.; Wang, X.; Chen, T. Facile and green reduction of covalently PEGylated nanographene oxide via a ‘water-only’ route for high-efficiency photothermal therapy. Nanoscale Res. Lett., 2014, 9(1), 86-96.
[http://dx.doi.org/10.1186/1556-276X-9-86] [PMID: 24548613]
[33]
Hummers, W.S.; Offeman, R.E. Preparation of graphitic oxide. J. Am. Chem. Soc., 1958, 80, 1339-1339.
[http://dx.doi.org/10.1021/ja01539a017]
[34]
Stobinski, L.; Lesiak, B.; Malolepszy, A.; Mazurkiewicz, M.; Mierzwa, B.; Zemek, J.; Jiricek, P.; Bieloshapka, I. Graphene oxide and reduced graphene oxide studied by the XRD, TEM and electron spectroscopy methods. J. Electron Spectrosc. Relat. Phenom., 2014, 195, 145-154.
[http://dx.doi.org/10.1016/j.elspec.2014.07.003]
[35]
Rampersad, S.N. Multiple applications of alamar blue as an indicator of metabolic function and cellular health in cell viability bioassays. Sensors (Basel), 2012, 12(9), 12347-12360.
[http://dx.doi.org/10.3390/s120912347] [PMID: 23112716]
[36]
D’Autréaux, B.; Toledano, M.B. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol., 2007, 8(10), 813-824.
[http://dx.doi.org/10.1038/nrm2256] [PMID: 17848967]
[37]
Chng, E.L.K.; Sofer, Z.; Pumera, M. Cytotoxicity profile of highly hydrogenated graphene. Chemistry, 2014, 20(21), 6366-6373.
[http://dx.doi.org/10.1002/chem.201304911] [PMID: 24711117]
[38]
De Marzi, L.; Ottaviano, L.; Perrozzi, F.; Nardone, M.; Santucci, S.; De Lapuente, J.; Borras, M.; Treossi, E.; Palermo, V.; Poma, A. Flake size-dependent cyto and genotoxic evaluation of graphene oxide on in vitro A549, CaCo2 and vero cell lines. J. Biol. Regul. Homeost. Agents, 2014, 28(2), 281-289.
[PMID: 25001660]
[39]
Seabra, A.B.; Paula, A.J.; de Lima, R.; Alves, O.L.; Durán, N. Nanotoxicity of graphene and graphene oxide. Chem. Res. Toxicol., 2014, 27(2), 159-168.
[http://dx.doi.org/10.1021/tx400385x] [PMID: 24422439]
[40]
Singh, S.K.; Singh, M.K.; Kulkarni, P.P.; Sonkar, V.K.; Grácio, J.J.; Dash, D. Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical applications. ACS Nano, 2012, 6(3), 2731-2740.
[http://dx.doi.org/10.1021/nn300172t] [PMID: 22376049]
[41]
Amrollahi-Sharifabadi, M.; Koohi, M.K.; Zayerzadeh, E.; Hablolvarid, M.H.; Hassan, J.; Seifalian, A.M. In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application. Int. J. Nanomedicine, 2018, 13, 4757-4769.
[http://dx.doi.org/10.2147/IJN.S168731] [PMID: 30174424]
[42]
Vallabani, N.V.; Mittal, S.; Shukla, R.K.; Pandey, A.K.; Dhakate, S.R.; Pasricha, R.; Dhawan, A. Toxicity of graphene in normal human lung cells (BEAS-2B). J. Biomed. Nanotechnol., 2011, 7(1), 106-107.
[http://dx.doi.org/10.1166/jbn.2011.1224] [PMID: 21485826]
[43]
Wang, A.; Pu, K.; Dong, B.; Liu, Y.; Zhang, L.; Zhang, Z.; Duan, W.; Zhu, Y. Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells. J. Appl. Toxicol., 2013, 33(10), 1156-1164.
[http://dx.doi.org/10.1002/jat.2877] [PMID: 23775274]
[44]
Yuan, X.; Liu, Z.; Guo, Z.; Ji, Y.; Jin, M.; Wang, X. Cellular distribution and cytotoxicity of graphene quantum dots with different functional groups. Nanoscale Res. Lett., 2014, 9(1), 108.
[http://dx.doi.org/10.1186/1556-276X-9-108] [PMID: 24597852]
[45]
Jaworski, S.; Sawosz, E.; Grodzik, M.; Winnicka, A.; Prasek, M.; Wierzbicki, M.; Chwalibog, A. In vitro evaluation of the effects of graphene platelets on glioblastoma multiforme cells. Int. J. Nanomedicine, 2013, 8, 413-420.
[PMID: 23378763]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 1
Year: 2020
Page: [47 - 58]
Pages: 12
DOI: 10.2174/1568009619666191021113807
Price: $65

Article Metrics

PDF: 29
HTML: 3