Skip to main content

Advertisement

Log in

Development of Graphene Oxide Nanosheets as Potential Biomaterials in Cancer Therapeutics: An In-Vitro Study Against Breast Cancer Cell Line

  • Published:
Journal of Inorganic and Organometallic Polymers and Materials Aims and scope Submit manuscript

Abstract

Recent advances in nanotechnology and nano biomaterials have attracted considerable attention in the field of cancer therapy. The development of biocompatible nanotherapeutics that selectively target cancer cells is a prime area of interest in current research. In the present study, graphene oxide nanosheets were synthesized using a modified Hummer’s method and characterized by using FTIR spectroscopy, Raman spectroscopy, and X-ray Diffraction analyses, FE-SEM, HR-TEM and AFM. FT-IR spectra revealed the presence of the characteristic wave-numbers of 1585 cm−1, 2841 cm−1, and 3443 cm−1 uncovering the presence of intrinsic functional groups predominantly C=C, C-O, and C=O bonds. The characteristic intrinsic defect proportions in the as-prepared GO sheets exhibited a portion of the ID/IG ratio of ~ 1.05, indicating thereby a lesser proportion of available defect quantity in our synthesized graphene oxide sheets. XRD studies uncovered an interesting characteristic value of (001) and (002) lattice planes at a diffraction angle of 30º, which indicated a crystalline nature of the as-prepared graphene sheets. Thermo Gravimetric analyses of the as-prepared sheets indicated that in the range of 300–900 ℃, the sheet exhibited a tremendous rate of thermal response at different applied temperatures, uncovering the underlying physico-chemical attributes of the sheets. It is observed from the DLS experimentation that GO sheets exhibited a zeta potential ζ-potential of − 9.3 mV, which is expected to be a most stable colloidal form. The lateral thickness of the graphene nanosheets was approximately 6.45 nm, which was corroborated by the TEM and AFM analyses, respectively. The potential biomedical application of graphene nanosheets was evaluated by assessing the cytotoxicity and antioxidant activity. The IC50 of H2O2 scavenging activity by GO sheets was determined to be 61.91 ± 1.14 µg/ml. The DPPH and H2O2 scavenging activity of the GO sheets increases with the increase with the dosage concentrations from 25 to 400 µg/ml, respectively. The in-vitro tests revealed that the GO sheets had a high level of cytotoxicity to the human breast cancer MDA-MB-231 cells that was concentration dependent. In contrast, the cytotoxicity of the GO sheets against the HaCaT normal cell line was marginal, suggesting that the graphene nanosheets could be safely used in cancer therapy.

Graphic Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. F. Tonelli, V. Goulart, K. Gomes, M. Ladeira, A. Santos, E. Lorençon, L. Ladeira, R. Resende, Graphene-based nanomaterials: biological and medical applications and toxicity. Nanomedicine 10, 2423–2450 (2015)

    Article  CAS  PubMed  Google Scholar 

  2. K. R. D. Kasibhatta, I. Madakannu, I. Prasanthi, Hetero atom doped graphene nanoarchitectonics as electrocatalysts towards the oxygen reduction and evolution reactions in acidic medium. J. Inorg. Organomet. Polym Mater. 31, 1859–1876 (2021)

    Article  CAS  Google Scholar 

  3. O. Akhavan, E. Ghaderi, Toxicity of graphene and graphene oxide nanowalls against bacteria. ACS Nano 4, 5731–5736 (2010)

    Article  CAS  PubMed  Google Scholar 

  4. E. Zaminpayma, P. Nayebi, M. Emami-Razavi, Electronic properties of the interface between metallic doped zigzag graphene and pristine graphene nanoribbons. J. Inorg. Organomet. Polym Mater. 30, 3694–3701 (2020)

    Article  CAS  Google Scholar 

  5. L. Feng, L. Wu, X. Qu, New horizons for diagnostics and therapeutic applications of graphene and graphene oxide. Adv. Mater. 25, 168–186 (2013)

    Article  CAS  PubMed  Google Scholar 

  6. D. Plach, J. Jampilek, Graphenic materials for biomedical applications. Nanomaterials 9, 1758 (2019)

    Article  CAS  Google Scholar 

  7. G. Lalwani, A. M. Khan, B. Sitharaman, S. Brook, S. Brook, Toxicology of Graphene-Based Nanomaterials. Adv Drug Deliv Rev 105, 109–144 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. C. Liu, J. Zhao, R. Zhang, H. Li, B. Chen, L. Zhang, H. Yang, Multifunctionalization of graphene and graphene oxide for controlled release and targeted delivery of anticancer drugs. Am. J. Transl. Res. 9, 5197–5219 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  9. A. D. Garg, D. V. Krysko, P. Vandenabeele, P. Agostinis, Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin. Cancer Immunol. Immunother. 61, 215–221 (2012)

    Article  CAS  PubMed  Google Scholar 

  10. J. Athinarayanan, V. S. Periasamy, K. A. Alatiah, M. A. Ahmed, A. A. Alshatwi, Green fabrication of Co3O4 nanoparticle-decorated reduced graphene oxide sheets: evaluation of biocompatibility on human mesenchymal stem cells for biomedical applications. J. Inorg. Organomet. Polym Mater. 27, 1110–1116 (2017)

    Article  CAS  Google Scholar 

  11. M. Grodzik, A. Winnicka, In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma. Int. J. Nanomed. 10, 1585–1596 (2015)

    Article  CAS  Google Scholar 

  12. Y. Chang, S. Yang, J. Liu, E. Dong, Y. Wang, A. Cao, Y. Liu, H. Wang, In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol. Lett. 200, 201–210 (2011)

    Article  CAS  PubMed  Google Scholar 

  13. M. Georgieva, B. Vasileva, G. Speranza, D. Wang, K. Stoyanov, M. Draganova-filipova, P. Zagorchev, V. Sarafian, G. Miloshev, N. Krasteva, Amination of graphene oxide leads to increased cytotoxicity in hepatocellular carcinoma cells. Int. J. Mol. 21, 2427 (2020)

    Article  CAS  Google Scholar 

  14. M. Kutwin, E. Sawosz, S. Jaworski, M. Wierzbicki, B. Strojny, M. Grodzik, M. E. Sosnowska, M. Trzaskowski, A. Chwalibog, Nanocomplexes of graphene oxide and platinum nanoparticles against colorectal cancer Colo205, HT-29, HTC-116, SW480, liver cancer HepG2, human breast cancer MCF-7, and adenocarcinoma LNCaP and human cervical Hela B cell lines. Materials (Basel) 12, 909 (2019)

    Article  CAS  Google Scholar 

  15. K. Chen, Y. Huang, J. Chen, Understanding and targeting cancer stem cells: therapeutic implications and challenges. Nat. Publ. Gr. 34, 732–740 (2013)

    CAS  Google Scholar 

  16. F. Safdari, H. Raissi, M. Shahabi, M. D. F. T. Zaboli, Calculations and molecular dynamics simulation study on the adsorption of 5-fluorouracil anticancer drug on graphene oxide nanosheet as a drug delivery vehicle. J. Inorg. Organomet. Polym Mater. 27, 805–817 (2017)

    Article  CAS  Google Scholar 

  17. J. Yan, T. Zhong, W. Qi, H. Wang, The application of assembled inorganic and organic hybrid nanoarchitecture of prussian blue/polymers/graphene in glucose biosensing. J. Inorg. Organomet. Polym Mater. 25, 275–281 (2015)

    Article  CAS  Google Scholar 

  18. S. Zinatloo-Ajabshir, S. AliHeidari-Asil, M. Salavati-Niasari, Simple and eco-friendly synthesis of recoverable zinc cobalt oxide-based ceramic nanostructure as high-performance photocatalyst for enhanced photocatalytic removal of organic contamination under solar light. Sep. Purif. Technol. 267, 118667 (2017)

    Article  CAS  Google Scholar 

  19. S. Zinatloo-Ajabshir, S. Ali Heidari-Asil, M. Salavati-Niasari, Recyclable magnetic ZnCo2O4-based ceramic nanostructure materials fabricated by simple sonochemical route for effective sunlight-driven photocatalytic degradation of organic pollution. Ceram. Int. 47, 8959–8972 (2021)

    Article  CAS  Google Scholar 

  20. S. Zinatloo-Ajabshir, M. Sadat Morassaei, M. Salavati-Niasari, Simple approach for the synthesis of Dy2Sn2O7 nanostructures as a hydrogen storage material from banana juice. J. Clean. Prod. 222, 103–110 (2019)

    Article  CAS  Google Scholar 

  21. S. Moshtaghi, S. Zinatloo-Ajabshir, M. Salavati-Niasari, Nanocrystalline barium stannate: facile morphology-controlled preparation, characterization and investigation of optical and photocatalytic properties. J. Mater. Sci. Mater. Electron. 27, 834–842 (2016)

    Article  CAS  Google Scholar 

  22. S. Zinatloo-Ajabshir, M. S. Morassaei, O. Amiri, M. Salavati-Niasari, Green synthesis of dysprosium stannate nanoparticles using Ficus carica extract as photocatalyst for the degradation of organic pollutants under visible irradiation. Ceram. Int. 46, 6095–6107 (2020)

    Article  CAS  Google Scholar 

  23. S. Zinatloo-Ajabshir, M. Baladi, M. Salavati-Niasari, Enhanced visible-light-driven photocatalytic performance for degradation of organic contaminants using PbWO4 nanostructure fabricated by a new, simple and green sonochemical approach. Ultrason. Sonochem. 72, 105420 (2021)

    Article  CAS  PubMed  Google Scholar 

  24. S. Zinatloo-Ajabshir, N. Ghasemian, M. Mousavi-Kamazani, M. Salavati-Niasari, Effect of zirconia on improving NOx reduction efficiency of Nd2Zr2O7 nanostructure fabricated by a new, facile and green sonochemical approach. Ultrason. Sonochem. 71, 105376 (2021)

    Article  CAS  PubMed  Google Scholar 

  25. S. Zinatloo-Ajabshir, M. Mousavi-Kamazani, Effect of copper on improving the electrochemical storage of hydrogen in CeO2 nanostructure fabricated by a simple and surfactant-free sonochemical pathway. Ceram. Int. 46, 26548–26556 (2020)

    Article  CAS  Google Scholar 

  26. M. Mousavi-Kamazani, S. Zinatloo-Ajabshir, M. Ghodrati, One-step sonochemical synthesis of Zn(OH)2/ZnV3O8 nanostructures as a potent material in electrochemical hydrogen storage. J. Mater. Sci. Mater. Electron. 31, 17332–17338 (2020)

    Article  CAS  Google Scholar 

  27. S. Zinatloo-Ajabshir, Z. Salehi, O. Amiri, M. Salavati-Niasari, Simple fabrication of Pr2Ce2O7 nanostructures via a new and eco-friendly route; a potential electrochemical hydrogen storage material. J. Alloys Compd. 791, 792–799 (2019)

    Article  CAS  Google Scholar 

  28. C. Donga, S. B. Mishra, A. S. Abd-El-Aziz, A. K. Mishra, Advances in graphene-based magnetic and graphene-based/TiO2 nanoparticles in the removal of heavy metals and organic pollutants from industrial wastewater. J. Inorg. Organomet. Polym Mater. 31, 463–480 (2021)

    Article  CAS  Google Scholar 

  29. D. Bitounis, H. Ali-boucetta, B. H. Hong, D. Min, Prospects and challenges of graphene in biomedical applications. Adv. Mater. 26, 2258–2268 (2013)

    Article  CAS  Google Scholar 

  30. S. M. Mousavi, S. A. Hashemi, Y. Ghasemi, M. Amani, A. Babapoor, O. Arjmand, Applications of graphene oxide in case of nanomedicines and nanocarriers for biomolecules : review study. Drug Metab. Rev. 0, 1–30 (2019)

    Google Scholar 

  31. P. D. Harvey, J. Plé, Recent advances in nanoscale metal–organic frameworks towards cancer cell cytotoxicity: an overview. J. Inorg. Organomet. Polym. Mater. (2021). https://doi.org/10.1007/s10904-021-02011-3

    Article  PubMed  PubMed Central  Google Scholar 

  32. J. Shen, M. Shi, N. Li, B. Yan, H. Ma, Y. Hu, M. Ye, Facile synthesis and application of Ag-chemically converted graphene nanocomposite. Nano Res. 3, 339–349 (2010)

    Article  CAS  Google Scholar 

  33. H. Liu, S. Hu, Y. Chen, S. Chen, Characterization and drug release behavior of highly responsive chip-like electrically modulated reduced graphene oxide – poly (vinyl alcohol) membranes. J. Mater. Chem. 22, 17311–17320 (2012)

    Article  CAS  Google Scholar 

  34. Y. Li, Y. Liu, Y. Fu, T. Wei, L. Le Guyader, G. Gao, R. Liu, Y. Chang, C. Chen, The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways. Biomaterials 33, 402–411 (2012)

    Article  PubMed  CAS  Google Scholar 

  35. L. Zhang, J. Xia, Q. Zhao, L. Liu, Z. Zhang, Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 6, 537–544 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. J. Liu, L. Cui, D. Losic, Graphene and graphene oxide as new nanocarriers for drug delivery applications. Acta Biomater. 9, 9243–9257 (2013)

    Article  CAS  PubMed  Google Scholar 

  37. K. Yang, S. Zhang, G. Zhang, X. Sun, S. Lee, Z. Liu, Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 10, 3318–3323 (2010)

    Article  CAS  PubMed  Google Scholar 

  38. P. Huang, C. Xu, J. Lin, C. Wang, X. Wang, C. Zhang, X. Zhou, S. Guo, Folic acid-conjugated graphene oxide loaded with photosensitizers for targeting photodynamic therapy. Theranostics 1, 240–250 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. E. L. Niero, B. Rocha-Sales, C. Lauand, B. A. Cortez, M. M. de Souza, P. Rezende-Teixeira, M. S. Urabayashi, A. A. Martens, J. H. Neves, G. M. Machado-Santelli, The multiple facets of drug resistance: one history, different approaches. J. Exp. Clin. Cancer Res. 33, 37 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. B. Zhang, P. Wei, Z. Zhou, T. Wei, Interactions of graphene with mammalian cells: Molecular mechanisms and biomedical insights. Adv. Drug Deliv. Rev. 105, 145–162 (2016)

    Article  CAS  PubMed  Google Scholar 

  41. B. F. M. Ribeiro, M. M. Souza, D. S. Fernandes, D. R. do Carmo, G. M. Machado-Santelli, Graphene oxide-based nanomaterial interaction with human breast cancer cells. J. Biomed. Mater. Res. - Part A 108, 863–870 (2020)

    Article  CAS  Google Scholar 

  42. N. Chatterjee, H. -J. Eom, Choi, J. , A systems toxicology approach to the surface functionality control of graphene-cell interactions. Biomaterials 35, 1109–1127 (2014)

    Article  CAS  PubMed  Google Scholar 

  43. N. I. Zaaba, K. L. Foo, U. Hashim, S. J. Tan, W. Liu, C. H. Voon, Synthesis of graphene oxide using modified hummers method: solvent influence. Proc. Eng. 184, 469–477 (2017)

    Article  CAS  Google Scholar 

  44. A. Bellova, E. Bystrenova, M. Koneracka, P. Kopcansky, F. Valle, N. Tomasovicova, M. Timko, J. Bagelova, F. Biscarini, Z. Gazova, Effect of Fe(3)O(4) magnetic nanoparticles on lysozyme amyloid aggregation. Nanotechnology 21, 65103 (2010)

    Article  CAS  Google Scholar 

  45. Q. Yuan, G. Zhou, L. Liao, Y. Liu, L. Luo, Interfacial structure in AZ91 alloy composites reinforced by graphene nanosheets. Carbon N. Y. 127, 177–186 (2017)

    Article  CAS  Google Scholar 

  46. M. Kashif, E. Jaafar, P. Bhadja, F. W. Low, S. K. Sahari, S. Hussain, F. K. Loong, A. Ahmad, T. S. AlGarni, M. Shafa et al., Effect of potassium permanganate on morphological, structural and electro-optical properties of graphene oxide thin films. Arab. J. Chem. 14, 102953 (2021)

    Article  CAS  Google Scholar 

  47. L. Bokobza, Some applications of vibrational spectroscopy for the analysis of polymers and polymer composites. Polymers (Basel) 11, 1159 (2019)

    Article  CAS  Google Scholar 

  48. A. Kołodziej, E. Długoń, M. Świętek, M. Ziąbka, E. Dawiec, M. Gubernat, M. Michalec, A. Wesełucha-Birczyńska, A Raman spectroscopic analysis of polymer membranes with graphene oxide and reduced graphene oxide. J. Compos. Sci. 5, 20 (2021)

    Article  CAS  Google Scholar 

  49. R. Muzyka, S. Drewniak, T. Pustelny, M. Sajdak, Ł Drewniak, Characterization of graphite oxide and reduced graphene oxide obtained from different graphite precursors and oxidized by different methods using Raman spectroscopy statistical analysis. Materials (Basel) 14, 769 (2021)

    Article  CAS  Google Scholar 

  50. H. Pan, S. Zhu, L. Mao, Graphene nanoarchitectonics: approaching the excellent properties of graphene from microscale to macroscale. J. Inorg. Organomet. Polym Mater. 25, 179–188 (2015)

    Article  CAS  Google Scholar 

  51. N. Kurnosov, V. Karachevtsev, Composite films of graphene oxide with semiconducting carbon nanotubes: Raman spectroscopy characterization. Low Temp. Phys. 47, 206–213 (2021)

    Article  CAS  Google Scholar 

  52. L. Chang, Y. Cao, W. Peng, C. Li, G. Fan, X. Song, C. Jia, Insight into the effect of oxidation degree of graphene oxides on their removal from wastewater via froth flotation. Chemosphere 262, 127837 (2021)

    Article  CAS  PubMed  Google Scholar 

  53. B. Ossonon, D. Bélanger, Synthesis and characterization of sulfophenyl-functionalized reduced graphene oxide sheets. RSC Adv. 7, 27224–27234 (2017)

    Article  CAS  Google Scholar 

  54. N. Pandey, C. Tewari, S. Dhali, B. S. Bohra, S. Rana, S. P. S. Mehta, S. Singhal, A. Chaurasia, N. G. Sahoo, Effect of graphene oxide on the mechanical and thermal properties of graphene oxide/hytrel nanocomposites. J. Thermoplast. Compos. Mater. 34, 55–67 (2021)

    Article  CAS  Google Scholar 

  55. S. A. Mousavi, M. Mehrpooya, Fabrication of copper centered metal organic framework and nitrogen, sulfur dual doped graphene oxide composite as a novel electrocatalyst for oxygen reduction reaction. Energy 214, 119053 (2021)

    Article  CAS  Google Scholar 

  56. S. M. Bhagyaraj, O. S. Oluwafemi, Nanotechnology: The Science of the Invisible. Synthesis of Inorganic Nanomaterials (Elsevier Ltd. , Amsterdam, 2018), pp. 1–18

    Book  Google Scholar 

  57. D. Titus, E. J. J. Samuel, S. M. Roopan, Nanoparticle Characterization Techniques (Elsevier Inc. , Amsterdam, 2019)

    Book  Google Scholar 

  58. S. Zhang, J. Li, G. Lykotrafitis, G. Bao, S. Suresh, Size-dependent endocytosis of nanoparticles. Adv Mater 21, 419–424 (2009)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. J. Linares, M. Concepcio, P. A. A. P. Marques, M. T. Portole, Endocytic mechanisms of graphene oxide nanosheets in osteoblasts, hepatocytes and macrophages. ACS Appl. Mater. Interfaces 6, 13697–13706 (2014)

    Article  CAS  PubMed  Google Scholar 

  60. E. Fröhlich, The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomed. 7, 5577–5591 (2012)

    Article  Google Scholar 

  61. Q. Yang, W. Zhongying, A. C. E. Owensa, I. Kulaotsa, Y. Chen, A. B. Kane, R. H. Hurt, Antioxidant chemistry of graphene-based materials and its role in oxidation protection technology. Nanoscale 6, 11744–11755 (2015)

    Google Scholar 

  62. M. S. Blois, Antioxidant determinations by the use of a stable free radical. Nature 181, 1199–1200 (1958)

    Article  CAS  Google Scholar 

  63. Y. Lee, Y. Yoon, H. Yoon, S. Song, H. Park, Y. Y. Lee, H. Shin, S. W. Hwang, K. Yeum, Enhanced antioxidant activity of bioactives in colored grains by nano-carriers in human lens epithelial cells. Molecules 23, 1327 (2018)

    Article  PubMed Central  CAS  Google Scholar 

  64. D. Suresh, M. A. P. Kumar, H. Nagabhushana, S. C. Sharma, Cinnamon supported facile green reduction of graphene oxide, its dye elimination and antioxidant activities. Mater. Lett. 151, 93–95 (2015)

    Article  CAS  Google Scholar 

  65. R. Rajeswari, H. G. Prabu, Synthesis characterization, antimicrobial, antioxidant, and cytotoxic activities of ZnO nanorods on reduced graphene oxide. J. Inorg. Organomet. Polym. Mater. (2017). https://doi.org/10.1007/s10904-017-0711-9

    Article  Google Scholar 

  66. L. Elias, R. Taengua, B. Frígols, B. Salesa, A. Serrano-Aroca, Carbon nanomaterials and led irradiation as antibacterial strategies against gram-positive multidrug-resistant pathogens. Int. J. Mol. Sci. 20, 3603 (2019)

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors would like to extend their sincere thanks to Natural and Medical Sciences Research Center, University of Nizwa, Oman. Authors would also like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research group NO (RGP-271).

Author information

Authors and Affiliations

Authors

Contributions

YKM and PRR were involved in the synthesis of GO nanosheets, antioxidant & MTT assays, and the preparation of the manuscript. KB, AKM, DD helped in the characterization of GO and drafting the manuscript. AH, AFA AAA, and EF revised the manuscript, SM analyzed the data and revised the manuscript, TKM drafted and revised the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Yugal Kishore Mohanta.

Ethics declarations

Conflict of interest

Authors declare that there is no conflict of interest among the co-authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohanta, Y.K., Biswas, K., Rauta, P.R. et al. Development of Graphene Oxide Nanosheets as Potential Biomaterials in Cancer Therapeutics: An In-Vitro Study Against Breast Cancer Cell Line. J Inorg Organomet Polym 31, 4236–4249 (2021). https://doi.org/10.1007/s10904-021-02046-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10904-021-02046-6

Keywords

Navigation