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In vitro and in vivo safety profile assessment of graphene oxide decorated with different concentrations of magnetite

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Abstract

In the last years, graphene oxide (GO) has attracted a lot of attention as a highly versatile structure, allowing studies aiming its application as support for magnetic nanoparticles. Thus, a technique of incorporation of iron nanoparticles into a GO surface was used, avoiding harmful agents to the environment, corroborating with the concepts applied in green chemistry, since pollution and environment damage is increasing due to incorrect disposal. The GO and magnetite-functionalized graphene oxide were characterized by Fourier transform infrared, X-ray diffraction, and scanning electron microscopy. Through the characterization techniques, it was possible to verify the presence of magnetite coated on the GO surface and typical morphology of the magnetic nanocomposite (GO·Fe3O4). After the synthesis and characterization studies, the cytotoxic effect of all produced nanocomposites was analyzed through DNA-PicoGreen®, dichlorofluorescein diacetate, nitric oxide, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays. In addition, the ecotoxic activity evaluation was performed through bioassay employing Artemia salina. The results showed low cytotoxic activity and ecotoxicity of the nanomaterials compared to the respective controls, exhibiting toxicity only at higher concentrations. With these experimental data, it is possible to produce a non-toxic magnetic nanocomposite, capable of being removed from the environment, through the application of a magnetic field, not having acute toxicity in Artemia salina.

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References

  1. Hoseini-Ghahfarokhi M, Mirkiani S, Mozaffari N, Sadatlu MAA, Ghasemi A, Abbaspour S, Akbarian M, Farjadian F, Karimi M (2020) Applications of graphene and graphene oxide in smart drug/gene delivery: is the world still flat? Int J Nanomedicine 15:9469–9496. https://doi.org/10.2147/IJN.S265876

    Article  CAS  Google Scholar 

  2. Farjadian F, Abbaspour S, Sadatlu MAA, Mirkiani S, Ghasemi A, Hoseini-Ghahfarokhi M, Mozaffari N, Karimi M, Hamblin MR (2020) Recent developments in graphene and graphene oxide: properties, synthesis, and modifications: a review. ChemistrySelect 5(33):10200–10219. https://doi.org/10.1002/slct.202002501

    Article  CAS  Google Scholar 

  3. Rhoden CRB, Bruckmann FS, Salles TR, Kaufmann CG Jr, Mortari SR (2021) Study from the influence of magnetite onto removal of hydrochlorothiazide from aqueous solutions applying magnetic graphene oxide. J Water Process Eng 43:102262. https://doi.org/10.1016/j.jwpe.2021.102262

    Article  Google Scholar 

  4. Salles TR, Rodrigues HB, Bruckmann FS, Alves LCS, Mortari SR, Rhoden CRB (2020) Graphene oxide optimization synthesis for application on laboratory of Universidade Franciscana. Discip Sci Ser Cienc Nat Tecnol 21:15–26. https://doi.org/10.37779/nt.v21i3.3632

    Article  Google Scholar 

  5. Liu S, Zeng TH, Hofmann M, Burcombe E, Wei J, Jiang R, Kong J, Chen Y (2011) Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. ACS Nano 5(9):6971–6980. https://doi.org/10.1021/nn202451x

    Article  CAS  Google Scholar 

  6. Ye S, Shao K, Li Z, Guo N, Zuo Y, Li Q, Lu Z, Chen L, He Q, Han H (2015) Antiviral activity of graphene oxide: how sharp edged structure and charge matter. ACS Appl Mater Interfaces 7(38):21571–21579. https://doi.org/10.1021/acsami.5b06876

    Article  CAS  Google Scholar 

  7. Yang XX, Li CM, Li YF, Wang J, Huang CZ (2017) Synergistic antiviral effect of curcumin functionalized graphene oxide against respiratory syncytial virus infection. Nanoscale 9(41):16086–16092. https://doi.org/10.1039/C7NR06520E

    Article  CAS  Google Scholar 

  8. Sharma G, Sharma S, Kumar A, Ala’a H, Naushad M, Ghfar AA, Mola GT, Stadler FJ (2018) Guar gum and its composites as potential materials for diverse applications: a review. Carbohydr Polym 199:534–545. https://doi.org/10.1016/j.carbpol.2018.07.053

    Article  CAS  Google Scholar 

  9. Adel R, Ebrahim S, Shokry A, Soliman M, Khalil M (2021) Nanocomposite of CuInS/ZnS and nitrogen-doped graphene quantum dots for cholesterol sensing. ACS Omega 6(3):2167–2176. https://doi.org/10.1021/acsomega.0c05416

    Article  CAS  Google Scholar 

  10. Shokry A, Khalil MMA, Ibrahim H, Soliman M, Ebrahim S (2019) Highly luminescent ternary nanocomposite of polyaniline, silver nanoparticles and graphene oxide quantum dots. Sci Rep 9(1):1–12. https://doi.org/10.1038/s41598-019-53584-6

    Article  CAS  Google Scholar 

  11. Ebrahim S, Shokry A, Khali MMA, Ibrahim H, Soliman M (2020) Polyaniline/Ag nanoparticles/graphene oxide nanocomposite fluorescent sensor for recognition of chromium (VI) ions. Sci Rep 10(1):1–11. https://doi.org/10.1038/s41598-020-70678-8

    Article  CAS  Google Scholar 

  12. Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Geilich BM, Webster TJ (2014) Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications. Int J Nanomedicine 9:3801–3814. https://doi.org/10.2147/IJN.S61143

    Article  CAS  Google Scholar 

  13. Bruckmann FS, Pimentel AC, Viana AR, Salles TR, Krause LMF, Mortari SR, Silva IZ, Rhoden CRB (2020) Synthesis, characterization, and cytotoxicity evaluation of magnetic nanosilica in L929 cell line. Discip Sci Ser Cienc Nat Tecnol. 21:1–14. https://doi.org/10.37779/nt.v21i3.3631

    Article  Google Scholar 

  14. Salles TR, Bruckamann FS, Viana AR, Krause LMF, Mortari SR, Rhoden CRB (2022) Magnetic nanocrystalline cellulose: azithromycin adsorption and in vitro biological activity against melanoma cells. J Polym Environ 30(2):1–19. https://doi.org/10.1007/s10924-022-02388-3

    Article  CAS  Google Scholar 

  15. Shokry A, El Tahan A, Ibrahim H, Soliman M, Ebrahim S (2019) The development of a ternary nanocomposite for the removal of Cr (VI) ions from aqueous solutions. RSC Adv 9(67):39187–39200. https://doi.org/10.1039/C9RA08298K

    Article  CAS  Google Scholar 

  16. Ebrahim S, Shokry A, Ibrahim H, Soliman M (2016) Polyaniline/akaganéite nanocomposite for detoxification of noxious Cr (VI) from aquatic environment. J Polym Res 23(4):1–11. https://doi.org/10.1007/s10965-016-0977-6

    Article  CAS  Google Scholar 

  17. Shokry A, El-Tahan A, Ibrahim H, Soliman M, Ebrahim S (2019) Polyaniline/akaganéite superparamagnetic nanocomposite for cadmium uptake from polluted water. Desalin Water Treat 171:205–215. https://doi.org/10.5004/dwt.2019.24835

    Article  CAS  Google Scholar 

  18. Serrano-Luján L, Víctor-Román S, Toledo C, Sanahuja-Parejo O, Mansour AE, Abad J, Amassian A, Benito AM, Mase WK, Urbina A (2019) Environmental impact of the production of graphene oxide and reduced graphene oxide. SN Applied Sciences 1(2):1–12. https://doi.org/10.1007/s42452-019-0193-1

    Article  CAS  Google Scholar 

  19. Cheng Y, Yang S, Tao E (2021) Magnetic graphene oxide prepared via ammonia coprecipitation method: the effects of preserved functional groups on adsorption property. Inorg Chem Commun 128:108603. https://doi.org/10.1016/j.inoche.2021.108603

    Article  CAS  Google Scholar 

  20. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  Google Scholar 

  21. Ahn SJ, Costa J, Rettig EJ (1996) PicoGreen quantitation of DNA: effective evaluation of samples pre-or psost-PCR. Nucleic acids Res 24(13):2623–2625. https://doi.org/10.1093/nar/24.13.2623

    Article  CAS  Google Scholar 

  22. Choi WS, Shin PG, Lee JH, Kim GD (2012) The regulatory effect of veratric acid on NO production in LPS-stimulated RAW264.7 marophage cells. Cell Immunol 280(2):164–170. https://doi.org/10.1016/j.cellimm.2012.12.007

    Article  CAS  Google Scholar 

  23. Krishna IV, Vanaja GR, Kumar NSK, Suman G (2009) Cytotoxic studies of anti-neoplastic drugs on human lymphocytes- in vitro studies. Cancer Biomark 5(6):261–272. https://doi.org/10.3233/CBM-2009-0111

    Article  CAS  Google Scholar 

  24. Abudabbus MM, Jevremović I, Janković A, Perić-Grujić A, Matić I, Vukašinović-Sekulić M, Hui D, Rhee KY, Mišković-Stanković V (2016) Biological activity of electrochemically synthesized silver doped polyvinyl alcohol/graphene composite hydrogel discs for biomedical applications. Compos B Eng 104:26–34. https://doi.org/10.1016/j.compositesb.2016.08.024

    Article  CAS  Google Scholar 

  25. Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277. https://doi.org/10.1016/0022-1759(86)90368-6

    Article  CAS  Google Scholar 

  26. Wilms LC, Hollman PCH, Boots AW, Kleinjans JCS (2005) Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes. Mutat Res 582(1–2):155–162. https://doi.org/10.1016/j.mrgentox.2005.01.006

    Article  CAS  Google Scholar 

  27. Santana DCN, Perina FC, Lourenço RA, da Silva J, Moreira LB, de Souza ADM (2021) Levels of hydrocarbons and toxicity of water-soluble fractions of maritime fuels on neotropical invertebrates. Ecotoxicology 30:2109–2118. https://doi.org/10.1007/s10646-021-02486-3

    Article  CAS  Google Scholar 

  28. Esmaeili Y, Bidram E, Zarrabi A, Amini A, Cheng C (2020) Graphene oxide and its derivatives as promising In-vitro bio-imaging platforms. Sci Rep 10(1):1–13. https://doi.org/10.1038/s41598-020-75090-w

    Article  CAS  Google Scholar 

  29. Bruckmann FS, Zuchetto T, Ledur CM, Santos CL, Silva WL, Fagan SB, Silva IZ, Rhoden CRB (2022) Methylphenidate adsorption onto graphene derivatives: theory and experiment. New J Chem 46(9):4283–4291. https://doi.org/10.1039/D1NJ03916D

    Article  CAS  Google Scholar 

  30. Bruckmann FS, Viana AR, Lopes LQS, Santos RCV, Muller EI, Mortari SR, Rhoden CRB (2022) Synthesis, characterization, and biological activity evaluation of magnetite-functionalized eugenol. J Inorg Organomet Polym 32(1):1–14. https://doi.org/10.1007/s10904-021-02207-7

    Article  CAS  Google Scholar 

  31. da Silva BF, Ledur CM, da Silva IZ, Dotto GL, Rhoden CRB (2022) A DFT theoretical and experimental study about tetracycline adsorption onto magnetic graphene oxide. J Mol Liq 353:118837. https://doi.org/10.1016/j.molliq.2022.118837

    Article  CAS  Google Scholar 

  32. Liu X, Shao XY, Fang GB, He HF, Wan ZG (2017) Preparation and properties of chemically reduced graphene oxide/copolymer-polyamide nanocomposites. e-Polymers 17(1):3–14. https://doi.org/10.1515/epoly-2016-0094

    Article  CAS  Google Scholar 

  33. Urbas K, Aleksandrzak M, Jedrzejczak M, Jedrzejczak M, Rakoczy R, Chen X, Mijowska E (2014) Chemical and magnetic functionalization of graphene oxide as a route to enhance its biocompatibility. Nanoscale Res Lett 9(1):1–12. https://doi.org/10.1186/1556-276X-9-656

    Article  CAS  Google Scholar 

  34. Gurunathan S, Arsalan Iqbal M, Qasim M, Park CH, Yoo H, Hwang JH, Uhm SJ, Song H, Park CH, Do JT, Choi Y, Kim JH, Hong K (2019) Evaluation of graphene oxide induced cellular toxicity and transcriptome analysis in human embryonic kidney cells. Nanomaterials 9(7):969. https://doi.org/10.3390/nano9070969

    Article  CAS  Google Scholar 

  35. Gholami A, Emadi F, Amini A, Shokripour M, Chashmpoosh M, Omidifar N (2020) Functionalization of graphene oxide nanosheets can reduce their cytotoxicity to dental pulp stem cells. J Nanomater 2020:6942707. https://doi.org/10.1155/2020/6942707

    Article  CAS  Google Scholar 

  36. Serth J, Kuczyk MA, Paeslack U, Lichtinghagen R, Jonas U (2000) Quantitation of DNA 753 extracted after micropreparation of cells from frozen and formalin-fixed tissue sections. Am J Pathol 156:1189–1196. https://doi.org/10.1016/S0002-9440(10)64989-9

    Article  CAS  Google Scholar 

  37. Lategan K, Alghadi H, Bayati M, Cortalezzi D, Fidalgo M, Pool E (2018) Effects of graphene oxide nanoparticles on the immune system biomarkers produced by RAW 264.7 and human whole blood cell cultures. Nanomaterials 8(2):125. https://doi.org/10.3390/nano8020125

    Article  CAS  Google Scholar 

  38. Zhang J, Eyisoylu H, Qin X, Rubert M, Muller R (2021) 3D bioprinting of graphene oxide-incorporated cell-laden bone mimicking scaffolds for promoting scaffold fidelity, osteogenic differentiation and mineralization. Acta Biomaterilia 121:637–652. https://doi.org/10.1016/j.actbio.2020.12.026

    Article  CAS  Google Scholar 

  39. Magaz A, Li X, Gough J, Blaker J (2020) Graphene oxide and electroactive reduced graphene oxide-based composite fibrous scaffolds for engineering excitable nerve tissue. Mater Sci Eng C 119:11632. https://doi.org/10.1016/j.msec.2020.111632

    Article  CAS  Google Scholar 

  40. Nair M, Nancy D, Krishnan AG, Anjusree GS, Vadukumpully S, Nair S (2015) Graphene oxide nano flakes incorporated gelatin – hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells. Nanotechnology 26(16):1–10. https://doi.org/10.1088/0957-4484/26/16/161001

    Article  CAS  Google Scholar 

  41. Wang A, Pu K, Dong B, Liu Y, Zhang L, Zhang Z, Duan W, Zhu Y (2013) Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells. J Appl Toxicol 33(10):1156–1164. https://doi.org/10.1002/jat.2877

    Article  CAS  Google Scholar 

  42. Zhang X, Hu W, Li J, Tao L, Wei Y (2012) A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond. Toxicol Res 1(62):62–68. https://doi.org/10.1039/c2tx20006f

    Article  CAS  Google Scholar 

  43. Carvalho JFD, Azevedo ÍMD, Rocha KBF, Medeiros AC, Carriço ADS (2017) Oxacillin magnetically targeted for the treatment of methicillin-resistant S. aureus infection in rats. Acta Cir Bras 32:46–55. https://doi.org/10.1590/s0102-865020170106

    Article  Google Scholar 

  44. Liao K, Lin Y, Macosko CW, Haynes C (2011) Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater Interfaces 3(7):2607–2615. https://doi.org/10.1021/am200428v

    Article  CAS  Google Scholar 

  45. Moise S, Cespedes E, Soukup D, Byrne JM, Haj AJ, Telling ND (2017) The cellular magnetic response and biocompatibility of biogenic zinc- and cobalt-doped magnetite nanoparticles. Sci Rep 7(39922):1–11. https://doi.org/10.1038/srep39922

    Article  CAS  Google Scholar 

  46. Jin L, Yue D, Xu ZW, Liang G, Zhang Y, Zhang JF, Zhang X, Wang Z (2014) Fabrication, mechanical properties, and biocompatibility of reduced graphene oxide- reinforced nanofiber mats. RSC Adv 4(66):35035–35041. https://doi.org/10.1039/C4RA03987D

    Article  CAS  Google Scholar 

  47. Nair M, Nancy D, Krishnan AG, Anjusree GS, Vadukumpully S, Nair SV (2015) Graphene oxide nanoflakes incorporated gelatin–hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells. Nanotechnology 26(16):161001. https://doi.org/10.1088/0957-4484/26/16/161001

    Article  CAS  Google Scholar 

  48. Wang A, Pu K, Dong B, Liu Y, Zhang L, Zhang Z, Duan W, Zhu Y (2013) Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fi broblast cells. J Appl Toxicol 33(10):1156–1164. https://doi.org/10.1002/jat.2877

    Article  CAS  Google Scholar 

  49. Ahmad J, Alhadlaq HA, Alshamsan A, Siddiqui MA, Saquib Q, Khan ST, Wabah R, Khedhairy A, Musarrat J, Akhatar MJ, Ahamed M (2016) Differential cytotoxicity of copper ferrite nanoparticles in different human cells. J Appl Toxicol 36(10):1284–1293. https://doi.org/10.1002/jat.3299

    Article  CAS  Google Scholar 

  50. Alhadlaq HA, Akhtar MJ, Ahamed M (2015) Zinc ferrite nanoparticle induced cytotoxicity and oxidative stress in different human cells. Cell Biosci 5(55):1–11. https://doi.org/10.1186/s13578-015-0046-6

    Article  CAS  Google Scholar 

  51. Hashemi E, Akhavan O, Shamsara M, Rahighi R, Esfandiar A, Tayefeh AR (2014) Cyto and genotoxicities of graphene oxide and reduced graphene oxide sheets on spermatozoa. RSC Adv 4(52):27213–27223. https://doi.org/10.1039/C4RA01047G

    Article  CAS  Google Scholar 

  52. Hajipour MJ, Raheb J, Akhavan O, Arjmand S, Mashinchian O, Rahman M, Abdolahad M, Serpooshan V, Laurent S (2015) Mahmoudi, M (2015) Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide. Nanoscale 7(19):8978–8994. https://doi.org/10.1039/C5NR00520E

    Article  CAS  Google Scholar 

  53. Costa CR, Olivi P, Botta CM, Espindola EL (2008) A toxicidade em ambientes aquáticos: discussão e métodos de avaliação. Quim Nova 31:1820–1830. https://doi.org/10.1590/S0100-40422008000700038

    Article  CAS  Google Scholar 

  54. Vimercati L, Cavone D, Caputi A, De Maria L, Tria M, Prato E, Ferri GM (2020) Nanoparticles: an experimental study of zinc nanoparticles toxicity on marine crustaceans. General overview on the health implications in humans. Public Health Front 8:192. https://doi.org/10.3389/fpubh.2020.00192

    Article  Google Scholar 

  55. Shokry A, Khalil M, Ibrahim H, Soliman M, Ebrahim S (2021) Acute toxicity assessment of polyaniline/Ag nanoparticles/graphene oxide quantum dots on Cypridopsis vidua and Artemia salina. Sci Rep 11(1):1–9. https://doi.org/10.1038/s41598-021-84903-5

    Article  CAS  Google Scholar 

  56. Rajabi S, Ramazani A, Hamidi M, Naji T (2015) Artemia salina as a model organism in toxicity assessment of nanoparticles. DARU J Pharm Sci 23(1):20–23. https://doi.org/10.1186/s40199-015-0105-x

    Article  CAS  Google Scholar 

  57. Krishnaraj C, Harper S, Yun S (2016) In Vivo toxicological assessment of biologically synthesized silver nanoparticles in adult Zebrafish (Danio rerio). J Hazard Mater 301:480–491. https://doi.org/10.1016/j.jhazmat.2015.09.022

    Article  CAS  Google Scholar 

  58. Mesarič T, Gambardella C, Milivojevic T, Faimali M, Drobne D, Falugi C, Makovec D, Jemec A, Sepcic K (2015) High surface adsorption properties of carbon-based nanomaterials are responsible for mortality, swimming inhibition, and biochemical responses in Artemia salina larvae. Aquat Toxicol 163:121–129. https://doi.org/10.1016/j.aquatox.2015.03.014

    Article  CAS  Google Scholar 

  59. Piccinetti CC, Montis C, Bonini M, Laurà R, Guerrera MC, Radaelli G, Vianello F, Santinelli V, Maradonna F, Nozzi V, Miccoli A, Olivotto I (2014) Transfer of silica-coated magnetic (Fe3O4) nanoparticles through food: a molecular and morphological study in zebrafish. Zebrafish 11(6):567–579. https://doi.org/10.1089/zeb.2014.1037

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank FAPERGS, CAPES, Laboratório de Materiais Magnéticos Nanoestruturados and Universidade Franciscana for the scholarships granted, and director Carlos Robalo/UFN for the support.

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de Oliveira, É.C., da Silva Bruckmann, F., Schopf, P.F. et al. In vitro and in vivo safety profile assessment of graphene oxide decorated with different concentrations of magnetite. J Nanopart Res 24, 150 (2022). https://doi.org/10.1007/s11051-022-05529-w

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