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PEGylation of graphene/iron oxide nanocomposite: assessment of release of doxorubicin, magnetically targeted drug delivery and photothermal therapy

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Abstract

Scientists have recommended to investigate graphene and graphene base compounds for their potential uses in a variety of fields, such as biomedicine and drug release. A PEGylated and functionalized magnetic graphene oxide (MG–NH2–PEG) complex was used herein as a nanocarrier of Doxorubicin, a cancer chemotherapy drug. First, graphene oxide was synthesized by modified Hummer’s method and then functionalized with amine groups (G–NH2). Afterwards, solvothermal of Fe3O4 magnetic nanoparticles on G–NH2 to prepare magnetic graphene oxide (MGO) modified by MG–NH2 via covalent bindings for the synthesis of MG–NH2–PEG. Doxorubicin (DOX) was loaded onto MG–NH2–PEG at pH 7 by the use of π–π interactions, yielding a highly significant value of DOX's loading efficiency along with its loading content. In vitro cytotoxicity tests on MCF-7 cells line were carried out for MG–NH2–PEG: DOX according to the drug loading and release characteristics. The results of standard MTT assay for the toxicity determination of both synthetic nanocomposites and the drug revealed over 85% of surviving cells after 48 h, with a cellular uptake of > 80%, suggesting a satisfactory outcome on the non-toxicity of the nanocomposite. It can, therefore, be concluded that MG–NH2–PEG showed to be an effective drug carrier in cancer chemotherapy drug delivery through loading the above drugs of low medicinal properties with individual dependency on pH levels. Furthermore, MG–NH2–PEG represent strong optical absorbance from the visible to the near-infrared (NIR) region, and can be utilized for localized photothermal ablation of cancer cells guided by the magnetic field.

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  • 09 April 2020

    The article PEGylation of graphen

References

  • Akbarzadeh A, Mikaeili H, Zarghami N, Mohammad R, Barkhordari A, Davaran S (2012) Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers. Int J Nanomed 7:511–526

    CAS  Google Scholar 

  • Akhavan O, Ghaderi E (2010) Toxicity of graphene and graphene oxide nanowalls against bacteria. ACS Nano 4(10):5731–5736

    Article  CAS  Google Scholar 

  • Angelopoulou A, Voulgari E, Diamanti EK, Gournis D, Avgoustakis K (2015) Graphene oxide stabilized by PLA-PEG copolymers for the controlled delivery of paclitaxel. Eur J Pharm Biopharm 93:18–26

    Article  CAS  Google Scholar 

  • Baniasadi H, Ramazani SA, Mashayekhan S, Ramezani Farani M, Ghaderinezhad F, Dabaghi M (2015) Design, fabrication, and characterization of novel porous conductive scaffolds for nerve tissue engineering. Int J Polym Mater Polym Biomater 64(18):969–977

    Article  CAS  Google Scholar 

  • Cole AJ, David AE, Wang J, Galbán CJ, Yang VC (2011) Magnetic brain tumor targeting and biodistribution of long-circulating PEG-modified, cross-linked starch-coated iron oxide nanoparticles. Biomaterials 32(26):6291–6301

    Article  CAS  Google Scholar 

  • Costantini S, Di Bernardo G, Cammarota M, Castello G, Colonna G (2013) Gene expression signature of human HepG2 cell line. Gene 518(2):335–345

    Article  CAS  Google Scholar 

  • Dinesh B, Devi KS, Kumar AS (2017) Curcumin-quinone immobilised carbon black modified electrode prepared by in-situ electrochemical oxidation of curcumin-phytonutrient for mediated oxidation and flow injection analysis of sulfide. J Electroanal Chem 804:116–127

    Article  CAS  Google Scholar 

  • Depan D, Shah J, Misra RDK (2011) Controlled release of drug from folate-decorated and graphene mediated drug delivery system: synthesis, loading efficiency, and drug release response. Mater Sci Eng C 31(7):1305–1312

    Article  CAS  Google Scholar 

  • Dissanayake NM, Current KM, Obare SO (2015) Mutagenic effects of iron oxide nanoparticles on biological cells. Int J Mol Sci 16(10):23482–23516

    Article  CAS  Google Scholar 

  • El-boubbou K (2018) Magnetic iron oxide nanoparticles as drug carriers: clinical relevance. Nanomedicine (Lond) 13(8):953–971. https://doi.org/10.2217/nnm-2017-0336

    Article  CAS  Google Scholar 

  • Farani R et al (2019) Extending the application of a magnetic PEG three-part drug release device on a graphene substrate for the removal of Gram-positive and Gram-negative bacteria and cancerous and pathologic cells. Drug Des Devel Ther 13:1581–1591

    Article  CAS  Google Scholar 

  • Feng L, Liu Z (2011) Graphene in biomedicine: opportunities and challenges. Nanomedicine 6(2):317–324

    Article  CAS  Google Scholar 

  • Gajendiran M, Jo H, Kim K (2019) Green synthesis of multifunctional PEG-carboxylate π back-bonded gold nanoconjugates for breast cancer treatment. Int J Nanomed. https://doi.org/10.2147/IJN.S190946

    Article  Google Scholar 

  • Garg B, Bisht T, Ling YC (2015) Graphene-based nanomaterials as efficient peroxidase mimetic catalysts for biosensing applications: an overview. Molecules 20(8):14155–14190

    Article  CAS  Google Scholar 

  • Ge J et al (2014) A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation. Nat Commun 5:4596

    Article  CAS  Google Scholar 

  • Guo L et al (2016) Prostate cancer targeted multifunctionalized graphene oxide for magnetic resonance imaging and drug delivery. Carbon N Y 107:87–99

    Article  CAS  Google Scholar 

  • Hong BJ, Compton OC, An Z, Eryazici I, Nguyen ST (2011) Successful stabilization of graphene oxide in electrolyte solutions: enhancement of bio-functionalization and cellular uptake. ACS Nano 127:1–10

    Google Scholar 

  • Huang J et al (2012) Mechanism of cellular uptake of graphene oxide studied by surface-enhanced Raman spectroscopy. Small 8(16):2577–2584

    Article  CAS  Google Scholar 

  • Hu CS, Tang SL, Chiang CH, Hosseinkhani H, Da Hong P, Yeh MK (2014) Characterization and anti-tumor effects of chondroitin sulfate–chitosan nanoparticles delivery system. J Nanoparticle Res 16(11):2672

    Article  Google Scholar 

  • Jiang F et al (2013) Eco-friendly synthesis of size-controllable amine-functionalized graphene quantum dots with antimycoplasma properties. Nanoscale 5(3):1137

    Article  CAS  Google Scholar 

  • Kim Y, Kim M, Min D (2011) Biocompatible reduced graphene oxide prepared by using dextran as a multifunctional reducing agent w. 3195–3197

  • Kumawat MK, Thakur M, Gurung RB, Srivastava R (2017) Graphene quantum dots from mangifera indica: application in near-infrared bioimaging and intracellular nano-thermometry. ACS Sustain Chem Eng 5(2):1382–1391. https://doi.org/10.1021/acssuschemeng.6b01893

    Article  CAS  Google Scholar 

  • Kiew SF et al (2017) Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability. Int J Pharm 534(1–2):297–307

    Article  CAS  Google Scholar 

  • Li S, Xiao L, Deng H, Shi X, Cao Q (2017) Remote controlled drug release from multi-functional Fe3O4/GO/Chitosan microspheres fabricated by an electrospray method. Colloids Surf B Biointerfaces 151:354–362

    Article  CAS  Google Scholar 

  • Lu Y-J, Wei K-C, Ma C-CM, Yang S-Y, Chen J-P (2012) Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes. Colloids Surf B Biointerfaces 89:1–9

    Article  CAS  Google Scholar 

  • Liu J, Dong J, Zhang T, Peng Q (2018) Graphene-based nanomaterials and their potentials in advanced drug delivery and cancer therapy. J. Control. Release 286(May):64–73

    Article  CAS  Google Scholar 

  • Liao KH, Lin YS, MacOsko CW, Haynes CL (2011) Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater. Interfaces 3(7):2607–2615

    Article  CAS  Google Scholar 

  • Ma X et al (2012) A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Res 5(3):199–212

    Article  CAS  Google Scholar 

  • Mehnati-najafabadi V, Taheri-kafrani A, Bordbar A (2018) Xylanase immobilization on modified superparamagnetic graphene oxide nanocomposite: effect of PEGylation on activity and stability. Int J Biol Macromol 107:418–425

    Article  CAS  Google Scholar 

  • Markovic ZM et al (2011) In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. Biomaterials 32(4):1121–1129

    Article  CAS  Google Scholar 

  • Marković ZM et al (2017) Ambient light induced antibacterial action of curcumin/graphene nanomesh hybrids. RSC Adv 7(57):36081–36092

    Article  Google Scholar 

  • Mendonça MCP et al (2016) PEGylation of reduced graphene oxide induces toxicity in cells of the blood-brain barrier: an in vitro and in vivo study. Mol Pharm 13(11):3913–3924

    Article  Google Scholar 

  • Mohammad-Taheri M, Vasheghani-Farahani E, Hosseinkhani H, Shojaosadati SA, Soleimani M (2012) Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran–spermine nanoparticle system. Iran Polym J 21(4):239–251

    Article  CAS  Google Scholar 

  • Ozcan F, Ersoz M, Yilmaz M (2009) Preparation and application of calix[4]arene-grafted magnetite nanoparticles for removal of dichromate anions. Mater Sci Eng C 29(8):2378–2383

    Article  CAS  Google Scholar 

  • Ordikhani F, Farani MR, Dehghani M, Tamjid E, Simchi A (2015) Physicochemical and biological properties of electrodeposited graphene oxide/chitosan films with drug-eluting capacity. Carbon 84:91–102

    Article  CAS  Google Scholar 

  • Qiao R et al (2018) Bioconjugation and Fluorescence Labelling of Iron Oxide Nanoparticles Grafted with Bromomaleimide- terminal Polymers. Biomacromol 19:4423–4429

    Article  CAS  Google Scholar 

  • Skwarecki AS, Milewski S, Schielmann M, Milewska MJ (2016) Antimicrobial molecular nanocarrier–drug conjugates. Nanomed Nanotechnol Biol Med 12(8):2215–2240

    Article  CAS  Google Scholar 

  • Sablok K, Bhalla V, Sharma P, Kaushal R, Chaudhary S, Suri CR (2013) Amine functionalized graphene oxide/CNT nanocomposite for ultrasensitive electrochemical detection of trinitrotoluene. J Hazard Mater 248–249(1):322–328

    Article  Google Scholar 

  • Singh SK, Singh MK, Kulkarni P, Sonkar VK, Gracio J (2012) Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical. ACS Nano 6(3):2731–2740

    Article  CAS  Google Scholar 

  • Su X, Tao J, Wang Q, Xu P, Luo W, Dang M, Wu J, Teng Z (2019) Controlled PEGylation of periodic mesoporous organosilica nanospheres for improving their stability in physiological solutions. Chin Chem Lett 30(4):929–932. https://doi.org/10.1016/j.cclet.2019.02.014

    Article  CAS  Google Scholar 

  • Sun X, Zebibula A, Dong X, Zhang G, Zhang D, Qian J, He S (2018) Aggregation-induced emission nanoparticles encapsulated with PEGylated nano graphene oxide and their applications in two-photon fluorescence bioimaging and photodynamic therapy in vitro and in vivo. ACS Appl Mater Interfaces 10(30):25037–25046. https://doi.org/10.1021/acsami.8b05546

    Article  CAS  Google Scholar 

  • Tao C, Zheng Q, An L, He M, Lin J, Tian Q, Yang S (2019) T 1-weight magnetic resonance imaging performances of iron oxide nanoparticles modified with a natural protein macromolecule and an artificial macromolecule. Nanomaterials (Basel) 92(2):170. https://doi.org/10.3390/nano9020170

    Article  CAS  Google Scholar 

  • Taylor P (2015) International journal of polymeric materials and design, fabrication, and characterization of novel porous conductive scaffolds for nerve tissue engineering design, fabrication, and characterization of novel porous conductive scaffolds for nerve tissue engineering 37–41.

  • Vila M, Portolés MT, Marques PA, Feito MJ, Matesanz MC, Ramírez-Santillán C, Gonçalves G, Cruz SM, Nieto A, Vallet-Regi M (2012) Cell uptake survey of pegylated nanographene oxide. Nanotechnology 23(46)

  • Wilding KM, Smith AK, Wilkerson JW, Bush DB, Knotts TA 4th, Bundy BC (2018) The locational impact of site-specific PEGylation: streamlined screening with cell-free protein expression and coarse-grain simulation. The locational impact of site-specific PEGylation: streamlined screening with cell-free protein expression and coarse-grain simulation. ACS Synth Biol 7(2):510–521. https://doi.org/10.1021/acssynbio.7b00316

    Article  CAS  Google Scholar 

  • Xie B et al (2017) Characterization of synergistic anti-tumor effects of doxorubicin and p53 via graphene oxide-polyethyleneimine nanocarriers. J Mater Sci. Technol 33(8):807–814

    Article  Google Scholar 

  • Yuan G, Yuan Y, Xu K, Luo Q (2014) Biocompatible PEGylated Fe3O4 nanoparticles as photothermal agents for near-infrared light modulated cancer therapy. Int J Mol Sci 15(10):18776–18788

    Article  Google Scholar 

  • Zhao X, Shang T, Zhang X, Ye T, Wang D, Rei L (2016) Passage of magnetic tat-conjugated Fe3O4@SiO2 nanoparticles across in vitro blood–brain barrier. Nanoscale Res Lett 11(1):451. https://doi.org/10.1186/s11671-016-1676-2

    Article  CAS  Google Scholar 

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Acknowledgements

The authors wish to acknowledge financial support provided for this work by the University of Tehran. Special thanks also go to the scientific help and guidance by Foad Soleimani, Mahan Rahmati, Ahmad Taiebi and Maryam Azarian.

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Authors and Affiliations

  1. School of Chemical Engineering, University College of Engineering, University of Tehran, Tehran, 4563-11155, Iran

    Marzieh Ramezani Farani & Parissa Khadiv-Parsi

  2. Institute of Biophysics and Biochemistry, University of Tehran, Tehran, 1417614411, Iran

    Gholam Hossein Riazi

  3. Department of Radio-Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran

    Mehdi Shafiee Ardestani

  4. Quantitative Medical Imaging Systems Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, 1417613151, Iran

    Hamidreza Saligheh Rad

  5. Medical Physics and Biomedical Engineering Department, Tehran University of Medical Sciences, Tehran, 1417613151, Iran

    Hamidreza Saligheh Rad

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  1. Marzieh Ramezani Farani
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  2. Parissa Khadiv-Parsi
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  3. Gholam Hossein Riazi
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  4. Mehdi Shafiee Ardestani
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Correspondence to Parissa Khadiv-Parsi or Mehdi Shafiee Ardestani.

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The original version of this article was revised: Due to open choice cancellation.

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Ramezani Farani, M., Khadiv-Parsi, P., Riazi, G. et al. PEGylation of graphene/iron oxide nanocomposite: assessment of release of doxorubicin, magnetically targeted drug delivery and photothermal therapy. Appl Nanosci 10, 1205–1217 (2020). https://doi.org/10.1007/s13204-020-01255-8

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