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Copolymer/graphene oxide nanocomposites as potential anticancer agents

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Abstract

A synthetic style for preparing a graphene oxide/poly(ethyleneglycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)2 nanocomposites (GO/PEG-b-poly(HEMA-g-LA)) is via reversible addition fragmentation chain transfer polymerization. The characterization of GO/PEG-b-poly(HEMA-g-LA)2 nanocomposites was confirmed by scanning electron microscopy, ultraviolet–visible (UV–Vis) spectroscopies and dynamic light scattering measurements. This system as a safe nanovehicle has been studied for cancer therapy. Adult male rats were randomly allocated into five groups. Rats received normal saline, doxorubicin (DOX 12 mg/kg), and GO/PEG-b-poly(HEMA-g-LA)2@DOX at 6, 12, or 24 mg/kg via intraperitoneal rout daily for 4 weeks. Finally, serum samples were obtained to determine serum biochemical parameters. After euthanasia, liver and kidney samples were preserved in formalin to perform histopathological analysis.

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References

  1. Cagel M, Grotz E, Bernabeu E, Moretton MA, Chiappetta DA (2017) Doxorubicin: nanotechnological overviews from bench to bedside. Drug Discov Today 22(2):270–281

    Article  CAS  PubMed  Google Scholar 

  2. Gabbia D, Canato E, Carraro V, Tomasini L, Guido M, Pasut G, De Martin S (2019) Novel super stealth immunoliposomes for cancer targeted delivery of doxorubicin: an innovative strategy to reduce liver toxicity. Dig Liver Dis 51:e21

    Article  Google Scholar 

  3. Nagiub M, Filippone S, Durrant D, Das A, Kukreja RC (2017) Long-acting PDE5 inhibitor tadalafil prevents early doxorubicin-induced left ventricle diastolic dysfunction in juvenile mice: potential role of cytoskeletal proteins. Can J Physiol Pharmacol 95(3):295–304

    Article  CAS  PubMed  Google Scholar 

  4. Superfin D, Iannucci AA, Davies AM (2007) Commentary: oncologic drugs in patients with organ dysfunction: a summary. Oncologist 12(9):1070–1083

    Article  CAS  PubMed  Google Scholar 

  5. Mobaraki M, Faraji A, Zare M, Dolati P, Ataei M, Manshadi HD (2017) Molecular mechanisms of cardiotoxicity: a review on major side-effect of doxorubicin. Indian J Pharm Sci 79:335–344

    Article  CAS  Google Scholar 

  6. Liu B, Zhou K (2019) Recent progress on graphene-analogous 2D nanomaterials: properties, modeling and applications. Prog Mater Sci 100:99–169

    Article  CAS  Google Scholar 

  7. Martín C, Kostarelos K, Prato M, Bianco A (2019) Biocompatibility and biodegradability of 2D materials: graphene and beyond. Chem Commun 55(39):5540–5546

    Article  Google Scholar 

  8. Chen XY, Low HR, Loi XY, Merel L, Mohd Cairul Iqbal MA (2019) Fabrication and evaluation of bacterial nanocellulose/poly(acrylic acid)/graphene oxide composite hydrogel: Characterizations and biocompatibility studies for wound dressing. J Biomed Mater Res Part B Appl Biomater 107(6):2140–2151

    Article  CAS  Google Scholar 

  9. Boehm HP, Setton R, Stumpp E (1986) Nomenclature and terminology of graphite intercalation compounds. Carbon 24(2):241–245

    Article  CAS  Google Scholar 

  10. Nemes-Incze P, Osváth Z, Kamarás K, Biró LP (2008) Anomalies in thickness measurements of graphene and few layer graphite crystals by tapping mode atomic force microscopy. Carbon 46(11):1435–1442

    Article  CAS  Google Scholar 

  11. Novoselov KS, Geim AK, Morozov SV, Jiang D, Zhang Y, Dubonos SV, Grigorieva IV, Firsov AA (2004) Electric field in atomically thin carbon films. Science 306(5696):666–669

    Article  CAS  PubMed  Google Scholar 

  12. IUPAC (1995) Recommended terminology for the description of carbon as a solid (IUPAC recommendations). Pure Appl Chem 67:491

    Google Scholar 

  13. Ivanovskii AL (2012) Graphene-based and graphene-like materials. Russ Chem Rev 81(7):571–605

    Article  CAS  Google Scholar 

  14. Avouris P, Dimitrakopoulos C (2012) Graphene: synthesis and applications. Mater Today 15(3):86–97

    Article  CAS  Google Scholar 

  15. Zhu Y, Murali S, Cai W, Li X, Suk JW, Potts JR, Ruoff RS (2010) Graphene and graphene oxide: synthesis, properties, and applications. Adv Mater (Weinheim, Germany) 22(35):3906–3924

    Article  CAS  Google Scholar 

  16. Novoselov KS, Fal’Ko VI, Colombo L, Gellert PR, Schwab MG, Kim K (2012) A roadmap for graphene. Nature 490(7419):192–200

    Article  CAS  PubMed  Google Scholar 

  17. Compton OC, Kim S, Pierre C, Torkelson JM, Nguyen ST (2010) Crumpled graphene nanosheets as highly effective barrier property enhancers. Adv Mater (Weinheim, Germany) 22(42):4759–4763

    Article  CAS  Google Scholar 

  18. Compton OC, Nguyen ST (2010) Graphene oxide, highly reduced graphene oxide, and graphene: versatile building blocks for carbon-based materials. Small 6(6):711–723

    Article  CAS  PubMed  Google Scholar 

  19. Dreyer DR, Park S, Bielawski CW, Ruoff RS (2010) The chemistry of graphene oxide. Chem Soc Rev 39(1):228–240

    Article  CAS  PubMed  Google Scholar 

  20. Lerf A, He H, Forster M, Klinowski J (1998) Structure of graphite oxide revisited. J Phys Chem B 102(23):4477–4482

    Article  CAS  Google Scholar 

  21. Pei S, Cheng HM (2012) The reduction of graphene oxide. Carbon 50(9):3210–3228

    Article  CAS  Google Scholar 

  22. Pei Z, Li L, Sun L, Zhang S, Shan XQ, Yang S, Wen B (2013) Adsorption characteristics of 1,2,4-trichlorobenzene, 2,4,6-trichlorophenol, 2-naphthol and naphthalene on graphene and graphene oxide. Carbon 51(1):156–163

    Article  CAS  Google Scholar 

  23. Brodie BC (1859) On the atomic weight of graphite. Philos Trans R Soc Lond 149:249–259

    Google Scholar 

  24. Staudenmaier L (1898) Verfahren zur darstellung der graphitsaure. Ber Dtsch Chem Ges 31:1481–1487

    Article  CAS  Google Scholar 

  25. Hummers WS Jr, Offeman RE (1958) Preparation of graphitic oxide. J Am Chem Soc 80(6):1339

    Article  CAS  Google Scholar 

  26. Krishnan D, Kim F, Luo J, Cruz-Silva R, Cote LJ, Jang HD, Huang J (2012) Energetic graphene oxide: challenges and opportunities. Nano Today 7(2):137–152

    Article  CAS  Google Scholar 

  27. Singh V, Joung D, Zhai L, Das S, Khondaker SI, Seal S (2011) Graphene based materials: past, present and future. Prog Mater Sci 56(8):1178–1271

    Article  CAS  Google Scholar 

  28. Bhasha S, Malik P, Jain P (2019) To study the effect of processing conditions on structural and mechanical characterization of graphite and graphene oxide-reinforced PVA nanocomposite. Polym Bull (Berlin) 76(8):3841–3855

    Article  CAS  Google Scholar 

  29. Chakraborty G, Pugazhenthi G, Katiyar V (2019) Exfoliated graphene-dispersed poly (lactic acid)-based nanocomposite sensors for ethanol detection. Polym Bull (Berlin) 76(5):2367–2386

    Article  CAS  Google Scholar 

  30. Dhanavel S, Revathy TA, Sivaranjani T, Sivakumar K, Palani P, Narayanan V, Stephen A (2020) 5-Fluorouracil and curcumin co-encapsulated chitosan/reduced graphene oxide nanocomposites against human colon cancer cell lines. Polym Bull (Berlin) 77(1):213–233

    Article  CAS  Google Scholar 

  31. Ebrahimpoor S, Kiarostami V, Khosravi M, Davallo M, Ghaedi A (2019) Bees metaheuristic algorithm with the aid of artificial neural networks for optimization of acid red 27 dye adsorption onto novel polypyrrole/SrFe < inf > 12 </inf > O<inf > 19 </inf >/graphene oxide nanocomposite. Polym Bull (Berlin) 76(12):6529–6553

    Article  CAS  Google Scholar 

  32. Ghahramani A, Gheibi M, Eftekhari M (2019) Polyaniline-coated reduced graphene oxide as an efficient adsorbent for the removal of malachite green from water samples. Polym Bull (Berlin) 76(10):5269–5283

    Article  CAS  Google Scholar 

  33. Gorbunova M, Komratova V, Grishchuk A, Badamshina E, Anokhin D (2019) The effect of addition of low-layer graphene nanoparticles on structure and mechanical properties of polyurethane-based block copolymers. Polym Bull (Berlin) 76(11):5813–5829

    Article  CAS  Google Scholar 

  34. Mindivan F, Göktaş M (2020) Preparation of new PVC composite using green reduced graphene oxide and its effects in thermal and mechanical properties. Polym Bull (Berlin) 77(4):1929–1949

    Article  CAS  Google Scholar 

  35. Ponnaiyan P, Nammalvar G (2019) Effect of additives on graphene oxide incorporated polysulfone (PSF) membrane. Polym Bull (Berlin) 76(8):4003–4015

    Article  CAS  Google Scholar 

  36. Sabet M, Soleimani H, Hosseini S (2020) Graphene impact of the LDPE characteristics. Polym Bull (Berlin) 77(1):459–474

    Article  CAS  Google Scholar 

  37. Srivastava J, Gupta N, Kushwaha A, Umrao S, Srivastava A, Singh M (2019) Highly sensitive and selective estimation of aspartame by chitosan nanoparticles–graphene nanocomposite tailored EQCM-MIP sensor. Polym Bull (Berlin) 76(9):4431–4449

    Article  CAS  Google Scholar 

  38. Thirukumaran P, Shakila Parveen A, Balasubramanian R, Ramkumar V, Selvamani A, Srinivasan VV, Babu CM, Kim SC (2019) Studies on graphene oxide/BMI-reinforced polybenzoxazine nanocomposites. Polym Bull (Berlin) 76(7):3733–3751

    Article  CAS  Google Scholar 

  39. Ussia M, Ruffino F, Bruno E, Spina E, Conticello I, Privitera V, Carroccio SC (2020) The role of solvent on the formulation of graphene/polyporphyrin hybrid material versus photocatalytic activity. Polym Bull (Berlin) 77(4):2073–2087

    Article  CAS  Google Scholar 

  40. Wei D, Luo X, Xiong L, Huang H, Li L, Yu X, Wei L (2019) High-performance poly(vinyl alcohol)–chitosan sponge modified with graphene oxide. Polym Bull (Berlin) 76(6):3059–3071

    Article  CAS  Google Scholar 

  41. Xiao D, He M, Liu Y, Xiong L, Zhang Q, Wei L, Li L, Yu X (2020) Strong alginate/reduced graphene oxide composite hydrogels with enhanced dye adsorption performance. Polym Bull. https://doi.org/10.1007/s00289-020-03105-7

    Article  Google Scholar 

  42. Yan L, Zhou Y, Zhang X, Zou H, Chen Y, Liang M (2019) Effect of graphene oxide with different exfoliation levels on the mechanical properties of epoxy nanocomposites. Polym Bull (Berlin) 76(12):6033–6047

    Article  CAS  Google Scholar 

  43. Gu Z, Zhu S, Yan L, Zhao F, Zhao Y (2019) Graphene-based smart platforms for combined cancer therapy. Adv Mater (Weinheim, Germany) 31(9):1800662

    Article  CAS  Google Scholar 

  44. Ma N, Song A, Li Z, Luan Y (2019) Redox-sensitive prodrug molecules meet graphene oxide: an efficient graphene oxide-based nanovehicle toward cancer therapy. ACS Biomater Sci Eng 5(3):1384–1391

    Article  CAS  PubMed  Google Scholar 

  45. Mousavi SM, Soroshnia S, Hashemi SA, Babapoor A, Ghasemi Y, Savardashtaki A, Amani AM (2019) Graphene nano-ribbon based high potential and efficiency for DNA, cancer therapy and drug delivery applications. Drug Metab Rev 51(1):91–104

    Article  CAS  PubMed  Google Scholar 

  46. Liang J, Huang Q, Hua C, Hu J, Chen B, Wan J, Hu Z, Wang B (2019) pH-responsive nanoparticles loaded with graphene quantum dots and doxorubicin for intracellular imaging, drug delivery and efficient cancer therapy. ChemistrySelect 4(20):6004–6012

    Article  CAS  Google Scholar 

  47. Ghamkhari A, Massoumi B, Jaymand M (2017) Novel ‘schizophrenic’ diblock copolymer synthesized via RAFT polymerization: poly(2-succinyloxyethyl methacrylate)-b-poly[(N-4-vinylbenzyl), N,N-diethylamine]. Des Monomers Polym 20(1):190–200

    Article  CAS  PubMed  Google Scholar 

  48. Rahdar A, Aliahmad M, Hajinezhad MR, Samani M (2018) Xanthan gum-stabilized nano-ceria: green chemistry based synthesis, characterization, study of biochemical alterations induced by intraperitoneal doses of nanoparticles in rat. J Mol Struct 1173:166–172

    Article  CAS  Google Scholar 

  49. Council NR (2011) Guide for the care and use of laboratory animals, 8th edn. The National Academies Press, Washington, DC

    Google Scholar 

  50. Ottewell PD, Mönkkönen H, Jones M, Lefley DV, Coleman RE, Holen I (2008) Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer. J Natl Cancer Inst 100:1167–1178

    Article  CAS  PubMed  Google Scholar 

  51. Dalske HF, Hardy K (1988) Effect of low-dose doxorubicin on calcium content and norepinephrine response in rat aorta. Eur J Cancer Clin Oncol 24:979–983

    Article  CAS  PubMed  Google Scholar 

  52. Zhang Q, Zhu S (2015) Ionic liquids: versatile media for preparation of vesicles from polymerization-induced self-assembly. ACS Macro Lett 4:755–758

    Article  CAS  PubMed  Google Scholar 

  53. Sun L, Wei H, Zhang X, Meng C, Kang GY, Ma W, Ma L, Wang B, Yu C (2020) Synthesis of polymeric micelles with a dual-functional sheddable PEG stealth for enhanced tumor-targeted drug delivery. Polym Chem. https://doi.org/10.1039/D0PY00653J

    Article  Google Scholar 

  54. Arica MY, Tuğlu D, Başar MM, Kilic D, Bayramoğlu G, Batislam E (2008) Preparation and characterization of infection-resistant antibiotics-releasing hydrogels rods of poly [hydroxyethyl methacrylate-co-(poly (ethylene glycol)-methacrylate]: biomedical application in a novel rabbit penile prosthesis model. J Biomed Mater Res B. 86:18–28

    Article  CAS  Google Scholar 

  55. Titelman GI, Gelman V, Bron S, Khalfin RL, Cohen YB, Bianco-Peled H (2005) Characteristics and microstructure of aqueous colloidal dispersions of graphite oxide. Carbon 43:641–649

    Article  CAS  Google Scholar 

  56. Vasile E, Pandele AM, Andronescu C, Selaru A, Dinescu S, Costache M, Hanganu A, Raicopol MD, Teodorescu M (2019) Hema-functionalized graphene oxide: a versatile nanofiller for poly (propylene fumarate)-based hybrid materials. Sci Rep 9:1–5

    Article  CAS  Google Scholar 

  57. Liu C, Li Y, Gao B, Li Y, Duan Q, Kakuchi T (2018) Comb-shaped, temperature-tunable and water-soluble porphyrin-based thermoresponsive copolymer for enhanced photodynamic therapy. Mater Sci Eng C 82:155–162

    Article  CAS  Google Scholar 

  58. Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–1003. https://doi.org/10.1038/nmat3776

    Article  CAS  PubMed  Google Scholar 

  59. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    Article  CAS  PubMed  Google Scholar 

  60. Higuchi T (1961) Rate of release of medicaments from ointments bases containing drugs in suspension. J Pharm Sci 50:874–875

    Article  CAS  PubMed  Google Scholar 

  61. Higuchi WI (1962) Analysis of data on the medicament release from ointments. J Pharm Sci 51(1962):802–804

    Article  CAS  PubMed  Google Scholar 

  62. Higuchi T (1963) Mechanism of sustained-action medication. J Pharm Sci 52:1145–1149

    Article  CAS  PubMed  Google Scholar 

  63. Hajinezhad MR, Jamshidian A, Samzadeh kermani A (2019) A comparative histopathological investigation of the effects of ZnO/chitosan nanocomposites and ZnO nanoparticles on thioacetamide-induced nephrophaty in rats. J Mazand Univ Med Sci 29(176):189–194

    Google Scholar 

  64. Kalaria DR, Sharma G, Beniwal V, Ravi Kumar MNV (2009) Design of biodegradable nanoparticles for oral delivery of doxorubicin: in vivo pharmacokinetics and toxicity studies in rats. Pharm Res 26(3):492–501

    Article  CAS  PubMed  Google Scholar 

  65. Yu J-M, Li Y-J, Qiu L-Y, Jin Y (2009) Polymeric nanoparticles of cholesterol-modified glycol chitosan for doxorubicin delivery: preparation and in vitro and in vivo characterization. J Pharm Pharmacol 61(6):713–719

    Article  CAS  PubMed  Google Scholar 

  66. Wohlfart S, Khalansky AS, Gelperina S, Maksimenko O, Bernreuther C, Glatzel M, Kreuter J (2011) Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers. PLoS ONE 6(5):e19121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ahmad N, Ahmad R, Alam MA, Ahmad FJ (2018) Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles. Chem Cent J 12(1):65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Petrovic D, Seke M, Borovic ML, Jovic D, Borisev I, Srdjenovic B, Rakocevic Z, Pavlovic V, Djordjevic A (2018) Hepatoprotective effect of fullerenol/doxorubicin nanocomposite in acute treatment of healthy rats. Exp Mol Pathol 104(3):199–211

    Article  CAS  PubMed  Google Scholar 

  69. Rahdar A, Taboada P, Aliahmad M, Hajinezhad MR, Sadeghfar F (2018) Iron oxide nanoparticles: synthesis, physical characterization, and intraperitoneal biochemical studies in Rattus norvegicus. J Mol Struct 1173:240–245

    Article  CAS  Google Scholar 

  70. Hajinezhad MR, Bameri S, Beyzaee H, Samzadeh-Kermani A (2020) Investigating the effects of long-term administration of green-synthetized nickel oxide (NiO) nanoparticles on liver, kidney and testis of rats. J Isfahan Med Sch 37:1226–1232

    Google Scholar 

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Acknowledgements

Authors would like to thank the Universities Zabol for financial support for this work. The biological part of this study was supported by the grant of University of Zabol (Grant Number 9618-15).

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Authors and Affiliations

  1. Department of Physics, University of Zabol, P. O. Box. 35856-98613, Zabol, Islamic Republic of Iran

    Abbas Rahdar

  2. Basic Veteinary Science Department, Veterinary Faculty, University of Zabol, Zabol, Iran

    Mohammad Reza Hajinezhad

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hamed Hamishekar

  4. Institute of Polymeric Materials, Faculty of Polymer Engineering, Sahand University of Technology, Tabriz, Iran

    Aliyeh Ghamkhari

  5. Department of Chemistry, International Hellenic University, 654 04, Kavala, Greece

    George Z. Kyzas

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  1. Abbas Rahdar
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  4. Aliyeh Ghamkhari
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Rahdar, A., Hajinezhad, M.R., Hamishekar, H. et al. Copolymer/graphene oxide nanocomposites as potential anticancer agents. Polym. Bull. 78, 4877–4898 (2021). https://doi.org/10.1007/s00289-020-03354-6

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