Bull. Mater. Sci. (2020) 43:42 © Indian Academy of Scienceshttps://doi.org/10.1007/s12034-019-1999-6

Synthesis and characterization of inherently radiopaquenanocomposites using biocompatible iodinated poly(methylmethacrylate-co-acrylamide) and graphene oxide

SAEED SHIRALIZADEH1, HOSSEIN NASR-ISFAHANI1, AMIR HOSSEIN AMIN1,MOSTAFA AZIMZADEH2,3,4 and RAMEZAN ALI TAHERI5,∗1School of Chemistry, Shahrood University of Technology, Shahrood, Iran2Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, ShahidSadoughi University of Medical Sciences, PO Box 89195-999, Yazd, Iran3Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of MedicalSciences, PO Box 89195-999, Yazd, Iran4Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University ofMedical Sciences, Yazd 8916188635, Iran5Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran∗Author for correspondence (taheri@bmsu.ac.ir)

MS received 1 March 2019; accepted 6 August 2019

Abstract. New inherently radiopaque nanocomposites were prepared using iodine-containing poly(methyl methacrylate-co-acrylamide) and graphene oxide. For this purpose, P(MMA-co-AA) was synthesized via copolymerization of methylmethacrylate and acrylic acid, and modified with 4-iodophenyl isocyanate and 3,4,5-triiodophenyl isocyanate to formpoly[(methyl methacrylate-co-(N-4-iodophenyl)acrylamide)] (1I-P(MMA-co-AA)) and poly[(methyl methacrylate-co-(N-3,4,5-triiodophenyl)acrylamide)] (3I-P(MMA-co-AA)), respectively. For comparative evaluation, the non-iodinatedcopolymer (PIC-P(MMA-co-AA)) was prepared via reaction of the P(MMA-co-AA) with phenyl isocyanate to investi-gate the effect of iodinated substituents on the morphology and thermal characteristics of the nanocomposites. All thenanocomposites were characterized by X-ray diffraction analysis, scanning electron microscopy, X-radiography and ther-mogravimetric analysis. The results proved that thermal properties of the nanocomposites improved by the introduction ofdifferent amounts of graphene oxide into the copolymers’ matrix. Radiopacity measurements showed the excellent radiopac-ity of iodinated nanocomposites and proved that 3I-GO-5 had radiopacity equivalent to that of an aluminium wedge with2-mm thickness.

Keywords. Radiopaque nanocomposite; iodine-containing polymer; methyl methacrylate; radiopacity; graphene oxide.

1. Introduction

Radiopaque polymers are the materials of choice for numerousbiomedical applications such as preparation of orthopaedicprosthesis, dental implants, embolization and drug deliv-ery systems. Radiopacity is the most important charac-teristic of radiopaque materials that facilitates investiga-tion of medical devices via the cheap and non-destructiveX-radiography technique [1–7]. Radiopaque materials canbe easily located via modern radiological diagnostic pro-cess. The usual polymers consist of elements such as C,H, N and O that have low electron density and low spe-cific gravity. Therefore, there is no significant contrast toX-ray. Many solutions have been investigated to overcomethis defect. Preparation of physical mixtures using poly-mers and metal powders or salts of heavy atoms is oneof the common approaches to fabricate radiopaque poly-mers [8,9]. Usually the bone cements contain micro-sized

filler particles such as barium sulphate and zirconium oxide.The main purpose of using these fillers is the modifi-cation of mechanical and radiopacity properties of thepolymers. However, heterogeneous dispersion and agglom-eration of the particles decrease fracture toughness of thecements. On the other hand, small size of fillers preservesmechanical characteristics as well as radiopacity of theproducts. For example, the effect of different morpholo-gies of filler on the mechanical and radiopacity propertiesof the polyurethane (PU)–BaSO4 nanocomposites has beeninvestigated [10,11]. The poly(amidoamine) dendrimers tem-plates have been designed for the synthesis of tin–dendrimernanocomposites and using them in the X-radiography pro-cess [12]. Various percentages of tantalum oxide (Ta2O5)

have been used in the glycerol dimethacrylate (GDMA) ora bisGMA, TEGDMA and bisEMA resin [13]. Hydroxyap-atite powder has been considered in restorative dentistry forthe preparation of the glass–polyalkenoate cement due to its

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biocompatibility, hardness and intrinsic radiopacity. Also, thenanohydroxyapatite–silica/glass ionomer cement has beensynthesized via sol–gel method [14,15]. The preparationof poly(vinyl acetate)/silver nanocomposite via suspensionpolymerization is used in the embolization process hasbeen investigated [16]. The embolic materials have beensynthesized based on poly(vinyl pivalate/vinyl acetate) andvarious radiopaque nanoparticles such as TiO2, Ti, Ag, Auand Pt [17]. Metal oxide mixtures such as Ta2O5/SiO2

[18,19], Yb2O3/SiO2 [20] and TiO2–SrO/nanotube havebeen used for the preparation of poly(methyl methacrylate)-based bone cements [21]. Tungsten nanoparticles have beenintroduced into the PU matrix to impart radiopacity tothe polymer [22]. However, in some cases, leaching outof the non-covalent radio-pacifying agents and heteroge-neous environment of these systems cause loss of bio-compatibility, physical and radiopacity properties of thefinal product. The preparation of complexes, via chelatingof polymeric ligands to heavy metal salts such as bis-muth bromide or uranyl nitrate, is another route to impartradiopacity to polymers. Copolymerization of metal saltsof vinyl monomers with other monomers has also beenconsidered, but the ionic nature of these radiopaque poly-mers leads to considerable water absorption and hydroly-sis of the final product [23–25]. Therefore, the substantialdeficiency of these radiopaque systems convinced the sci-entists to design and synthesize polymers with inherentradiopacity. In recent years, covalent binding of iodineatom to the monomers or polymers has been frequentlyconsidered. Due to the safety, excellent radiopacity, highstability and non-toxicity, the iodinated compounds arethe most widely used contrast agents for the synthesis ofradiopaque polymers [26,27]. Radiopaque materials are alsomade via grafting of iodinated substituents on the poly-mer chains or polymerization of iodine-containing monomers[11,28–30].

Since 2004, graphene has been the centre of interest dueto the superior characteristics. The large surface area, hightransparency, mechanical strength and thermal conductivityof graphene (and its derivatives) have brought it to a focalpoint in medicinal and industrial applications [31–35], and itis an ideal candidate for the synthesis of hybrid nanomaterialsused in diagnostic imaging process such as fluorescent imag-ing [36], magnetic resonance imaging (MRI) [37], computedtomography (CT) [38] and radionuclide imaging [39].

As a part of our interest in the synthesis and investi-gation of nanostructures [40–43], and due to the intrin-sic deficiency of the metal–polymer nanocomposites, inthis work, radiopaque nanocomposites were prepared usingiodine-containing poly(methyl methacrylate-co-acrylamide)and graphene oxide (GO) as the reinforcement agent. Basedon the previous work [29], methyl methacrylate and acrylicacid were copolymerized (P(MMA-co-AA)) and subsequen-tly reacted with 4-iodophenyl isocyanate and 3,4,5-triiodo-phenyl isocyanate as radio-pacifying agents to formpoly[(methyl methacrylate-co-(N-4-iodophenyl)acrylamide)]

Scheme 1. The synthesis route of P(MMA-co-AA), 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA).

(1I-P(MMA-co-AA)) and poly[(methylmethacrylate-co-(N-3,4,5-triiodophenyl)acrylamide)] (3I-P(MMA-co-AA),respectively. Thermal properties of radiopaque copolymerswere modified with various amounts of GO.

2. Experimental

2.1 Materials

GO (research-grade GO nanoplatelets, 99.5+%, and thick-ness 2–18 nm with less than 32 layers) was supplied fromUS Research Nanomaterials. Phenyl isocyanate (PIC) andacetone were obtained from Merck (Germany), and used asobtained. Toluene was purchased from Merck (Germany) anddried over sodium before use.

2.2 Synthesis of 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA)

Following a literature procedure [29], 1I-P(MMA-co-AA)and 3I-P(MMA-co-AA) were prepared through copolymer-ization of methyl methacrylate and acrylic acid and subse-quently modified with 4-iodophenyl isocyanate and 3,4,5-triiodophenyl isocyanate, respectively. For synthesis of iso-cyanate moieties, 4-iodobenzoyl azide and 3,4,5-triiodoben-zoyl azide were separately refluxed in dry toluene. Thesolutions obtained were cooled to room temperature and thenfiltered using a Buchner funnel. The filtrates were reacted withthe swelled P(MMA-co-AA) in dry toluene in an ice bath andAr atmosphere. The mixtures were stirred for 2 h at 0◦C andthen further for 5 h at 100◦C. The final products were obtainedas flexible precipitates, washed with toluene and dried at roomtemperature for 24 h.

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Figure 1. Schematic structure of the nanocomposites.

Table 1. Sample abbreviations.

Entry Copolymer Sample code GO (wt%)

1 PIC-P(MMA-co-AA) PIC-GO-X X = 1, 2, 5, 102 1I-P(MMA-co-AA) 1I-GO-X3 3I-P(MMA-co-AA) 3I-GO-X

2.3 Synthesis of poly[(methyl methacrylate-co-(N-phenyl)acrylamide)] (PIC-P(MMA-co-AA))

A 3 g of the swelled P(MMA-co-AA) in dry toluene wasmade to react with 20 ml PIC at 0◦C in Ar atmosphere. Themixture was stirred in an ice bath for 2 h; later the temperaturewas slowly raised to 100◦C, and the reaction continued for5 h at this temperature. The final product was isolated as aflexible precipitate, washed with toluene and dried at roomtemperature for 24 h.

2.4 Preparation of nanocomposites

Various amounts of GO (1, 2, 5, 10 wt%) were dispersedin 20 ml acetone using an ultrasonic homogenizer; 0.2 g ofPIC-P(MMA-co-AA), 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA) were separately dissolved in acetone and added to theGO suspensions. The mixtures were homogenized ultrason-ically and stirred at room temperature for 24 h. The solventwas evaporated at ambient pressure and the products weredried in a vacuum oven at 50◦C for 24 h.

3. Characterization

X-ray diffraction (XRD) analysis was performed on aSTOE-STADV (CuKα radiation, k = 0.15405 nm). The mor-phology of the nanocomposites was investigated using aVEGA\\TESCAN-XMU scanning electron microscope. Thethermogravimetric analysis (TGA) data for the polymers andnanocomposites were taken on a Mettler Toledo TGA 1 sys-tem in an N2 atmosphere at a heating rate of 10◦C min−1. TheX-radiographs were obtained using a standard clinical X-raymachine (Xgenus, DeGotzen, Italy) at 60 keV.

4. Results

Considering the importance of radiopaque materials in themedical fields, radiopaque nanocomposites were synthe-sized using iodine-containing poly(methyl methacrylate-co-acrylamide) and GO. For this purpose, the P(MMA-co-AA)was prepared via copolymerization of methyl methacrylateand acrylic acid in the presence of 2,2′-azobis(isobutyronitr-ile) (AIBN) as initiator. The P(MMA-co-AA) was reactedwith 4-iodophenyl isocyanate and 3,4,5-triiodophenyl isocya-nate to obtain 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA),respectively (scheme 1). For comparative evaluation andinvestigation of the effect of bulky iodine atoms on the proper-ties and morphology of the nanocomposites, the P(MMA-co-AA) was modified with PIC. The radiopaque nanocompositeswere characterized using TGA, XRD, scanning electronmicroscopy (SEM) and X-radiography. To investigate the

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Figure 2. XRD patterns of (a) PIC-GO-X nanocomposites, (b) 1I-GO-X nanocom-posites and (c) 3I-GO-X nanocomposites.

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Figure 3. SEM images of (a) PIC-P(MMA-co-AA), (b) PIC-GO-5, (c) PIC-GO-10, (d) 1I-P(MMA-co-AA),(e) 1I-GO-5, (f) 1I-GO-10, (g) 3I-P(MMA-co-AA), (h) 3I-GO-5 and (i) 3I-GO-10.

effect of filler amount on the thermal properties, variouspercentages of GO (1, 2, 5 and 10 wt%) were used for thesynthesis of the nanocomposites. The nanocomposites wereprepared via the solution method using acetone as the solvent(figure 1). The sample abbreviations are mentioned in table 1.

4.1 XRD analysis

The morphology and structure of the nanocomposites wereevaluated by XRD analysis. The XRD patterns of GO and thePIC-GO-X nanocomposites are shown in figure 2a. The basalpeak of GO emerged at an angle of 10.60◦, which is attributed

to the 8.37-nm d-spacing. As can be seen, this peak hasdiminished in the XRD patterns of the PIC-GO-X nanocom-posites. Similarly, the basal peak of GO is not visible in thediffraction patterns of the 1I-GO-X and 3I-GO-X nanocom-posites (figure 2b and c). These observations confirmedthat the PIC-P(MMA-co-AA), 1I-P(MMA-co-AA) and3I-P(MMA-co-AA) copolymers are structurally compati-ble with GO. In addition, the adaptability of the copoly-mers structure and GO has a considerable effect on thefinal structure of the nanocomposites. The d-spacing val-ues prove exfoliation and good dispersion of the GO layerswithin the PIC-P(MMA-co-AA), 1I-P(MMA-co-AA) and

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Figure 4. Thermal properties of PIC-P(MMA-co-AA), PIC-GO-1, PIC-GO-2 and PIC-GO-5.

3I-P(MMA-co-AA) polymer matrix. It was found that thelarge size of iodinated moieties on the copolymer chains playsan important role in the delamination of the GO sheets andsubsequent penetration of the chains into the GO galleries.

4.2 SEM

The surface structures of the nanocomposites and the purecopolymers were investigated by SEM (figure 3). The dis-persion of the GO layers into the matrix of the PIC-P(MMA-co-AA), 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA)

copolymers is confirmed well by the SEM images. Themicrographs show the considerable changes on the surfaceof the nanocomposites compared with the pure copolymers.Furthermore, there is no significant agglomeration of the GOlayers on increasing the amount of filler. These observationsproved the compatibility of the 1I-P(MMA-co-AA) and 3I-(MMA-co-AA) with the GO layers. Moreover, SEM imagesconfirmed the results of XRD analysis. As can be seen, pen-etration of the chains into the GO galleries led to exfoliationand good dispersion of the layers within the copolymers’matrix.

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Figure 5. Thermal properties of 1I-P(MMA-co-AA), 1I-GO-1, 1I-GO-2 and 1I-GO-5.

4.3 Thermal analysis

Thermal stabilities of the nanocomposites and the purecopolymers were measured via TGA. As shown in figure 4,the PIC-GO-X series have more thermal stability than thatof PIC-P(MMA-co-AA). The TGA graph of the PIC-GO-5 sample shows 5 and 10% weight loss at 180 and 201◦C,while the related values for the pure copolymer are about 152and 188◦C, respectively. Additionally, thermal behaviour ofthe samples containing 1 and 2 wt% of the filler improved

when compared with the pure copolymer. These observationsprove the effective interaction of the GO layers with the PIC-P(MMA-co-AA) chains.

Similarly, presence of GO sheets in the 1I-P(MMA-co-AA) matrix led to improved thermal stability of thecopolymer. According to the TGA results, the 1I-GO-1 sam-ple lost 5 and 10 wt% at 223 and 253◦C, respectively.These observations proved that thermal stability of 1I-GO-1is about 70◦C higher than that of pure 1I-P(MMA-co-AA)(figure 5).

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Figure 6. Thermal properties of 3I-P(MMA-co-AA), 3I-GO-1, 3I-GO-2 and 3I-GO-5.

The heat durability of the 3I-P(MMA-co-AA) copolymerhas also been improved by the introduction of the GO lay-ers into the copolymer matrix. The TGA results exhibited 5and 10% weight loss of the 3I-GO-1 sample at 277 and298◦C, which are about 70 and 100◦C more than thoseof the pure copolymer, respectively (figure 6). Thermal sta-bilities of the samples with 2 and 5 wt% loading of the GOhave also significantly increased. It was found that the GOsheets have a considerable effect on the thermal stability of the

3I-P(MMA-co-AA) stability even at high levels of loading.The results of thermal analysis are summarized in table 2.

4.4 Radiopacity

The X-ray visibilities of PIC-GO-5, 1I-GO-5 and 3I-GO-5 were evaluated by radiography technique and comparedto aluminium wedges with different thicknesses (0.5–3mm). All the samples were prepared as discs with 2-mm

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Table 2. Thermal characteristics of the pure copolymers and thenanocomposites.

Sample T5 (◦C) T10 (◦C)

PIC-P(MMA-co-AA) 152 188PIC-GO-1 177 225PIC-GO-2 177 216PIC-GO-5 180 2011I-P(MMA-co-AA) 150 2211I-GO-1 223 2531I-GO-2 161 2101I-GO-5 216 2483I-P(MMA-co-AA) 225 2883I-GO-1 277 2983I-GO-2 273 2983I-GO-5 260 291

thickness. The radiographic images prove that theiodine-containing nanocomposites have excellent radiopac-ity and contrast when compared with the PIC-GO-5 sample(non-iodinated nanocomposite, figure 7). The 3I-GO-5 sam-ple has the maximum contrast among the samples, which isequal to that of the 2-mm aluminium wedge. It is found thatheavy elements (iodine) have an important role in impart-ing radiopacity to the polymers and the radiopacity increaseson increasing the number of iodine atom in the structure ofpolymer.

5. Conclusion

New radiopaque nanocomposites were synthesized usingiodine-containing poly[(methyl methacrylate-co-(N-phenyl)acrylamide)] and GO as the reinforcement agent. The

radiopaque copolymers were prepared through two steps.The first step involves the copolymerization of methylmethacrylate and acrylic acid in the presence of AIBN.In the second step, P(MMA-co-AA) was reacted with 4-iodophenyl isocyanate and 3,4,5-triiodophenyl isocyanateseparately as the radio-pacifying agents for the synthe-sis of 1I-P(MMA-co-AA) and 3I-P(MMA-co-AA), respec-tively. To evaluate the effect of filler on the thermal prop-erties of the radiopaque copolymers, different amountsof GO (1, 2, 5 and 10 wt%) were used for the prepa-ration of the nanocomposites. PIC-P(MMA-co-AA) wasalso prepared via reaction of P(MMA-co-AA) with PICin order to investigate the effect of iodine atom on thethermal properties and morphology of the nanocomposites.The structure and morphology of the samples were anal-ysed by XRD and SEM techniques. The SEM images andXRD curves of the PIC-GO-X , 1I-GO-X and 3I-GO-Xnanocomposites proved complete exfoliation and signifi-cant distribution of the GO layers within the copolymersmatrices. Effective interactions between the GO layers andcopolymer chains were confirmed clearly by the results ofthe thermal analysis. The TGA and DTG curves showedthe higher thermal stability of the nanocomposites than thepure copolymers. These observations indicate the excellentstructural compatibility of the copolymers and the filler.The X-ray images show the superior radiopacity of theradiopaque nanocomposites. Due to the presence of threeiodine atoms in its repeating unit, the 3I-GO-5 sampleexhibits the maximum contrast rather than the other sam-ples, which is similar to the aluminium wedge with 2-mmthickness. It was found that higher number of iodine atomsin each repeating unit of a polymer has enhanced the X-rayvisibility.

Figure 7. X-ray images of aluminium wedge, (a) PIC-GO-5, (b) 1I-GO-5 and (c) 3I-GO-5.

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Acknowledgements

The authors would like to thank the ‘Clinical ResearchDevelopment Center of Baqiyatallah Hospital’ for their kindlycooperation. The financial support of Shahrood Universityof Technology is gratefully acknowledged (Grant Number50/3786).

References

[1] Wallyn J, Anton N, Serra C A, Bouquey M, Collot M, AntonH et al 2018 Acta Biomater. 66 200

[2] Kulcsár Z, Karol A, Kronen P W, Svende P, Klein K, Jordan Oet al 2017 Eur. Radiol. 27 1248

[3] Ashrafi K, Tang Y, Britton H, Domenge O, Blino D, BushbyA J et al 2017 J. Control Release 250 36

[4] Ma Q, Lei K, Ding J, Yu L and Ding J 2017 Polym. Chem. 86665

[5] Houston K R, Brosnan S M, Burk L M, Lee Y Z, Luft J C andAshby V S 2017 J. Polym. Sci. Polym. Chem. 55 2171

[6] Sang L, Luo D, Wei Z and Qi M 2017 Mater. Sci. Eng. C 751389

[7] Guo X, Johnson D P and Stehr R E 2017 US 0321054 A1[8] James N R and Jayakrishnan A 2007 Biomaterials 28 3182[9] Dawlee S, Jayakrishnan A and Jayabalan M 2009 J. Mater. Sci.

Mater. Med. 20 243[10] Gomoll A H, Bellare A, Fitz W, Thornhill T S, Scott R D,

Jemian P R et al 1999 Mater. Res. Soc. Symp. Proc. 581 399[11] Romero-Ibarra I, Bonilla-Blancas E, Sanchez-Solis A and

Manero O 2012 Eur. Polym. J. 48 670[12] Ely T O, Sharma M, Lesniak W, Klippenstein D L, Foster B A

and Balogh L P 2007 Mater. Res. Soc. Symp. Proc. 1064 6[13] Chan D, Titus H, Chung K H, Dixon H, Wellinghoff S and

Rawls H 1999 Dent. Mater. 15 219[14] Nicholson J, Hawkins S and Smith J 1993 J. Mater. Sci. Mater.

Med. 4 418[15] Shiekh R A, Ab Rahman I and Luddin N 2014 Ceram. Int. 40

3165[16] Yeum J H, Sun Q and Deng Y 2005 Macromol. Mater. Eng.

290 78[17] Cha J W, Lyoo W S, Oh T H, Han S S and Lee H G 2014 Fiber.

Polym. 15 472[18] Schulz H, Pratsinis S E, Rüegger H, Zimmermann J, Klapdohr

S and Salz U 2008 Colloid Surf. Physicochem. Eng. Asp. 31579

[19] Schulz H, Mädler L, Pratsinis S E, Burtscher P and MosznerN 2005 Adv. Funct. Mater. 15 830

[20] Mädler L, Krumeich F, Burtscher P and Moszner N 2006 J.Nanopart. Res. 8 323

[21] Khaled S, Charpentier P A and Rizkalla A S 2010 Acta Bio-mater. 6 3178

[22] Hasan S M, Harmon G, Zhou F, Raymond J E, Gustafson T P,Wilson T S et al 2016 Polym. Adv. Tech. 27 195

[23] Ginebra M, Albuixech L, Fernandez-Barragan E, Aparicio C,Gil F, San Roman J et al 2002 Biomaterials 23 1873

[24] Deb S, Abdulghani S and Behiri J 2002 Biomaterials 23 3387[25] Cabasso I, Smid J and Sahni S K 1989 J. Appl. Polym. Sci. 38

1653[26] Ghosh P, Das M, Rameshbabu A P, Das D, Datta S, Pal S et al

2014 ACS Appl. Mater. Interfaces 6 17926[27] Boyde A, Mccorkell F A, Taylor G K, Bomphrey R J and Doube

M 2014 Microsc. Res. Tech. 77 1044[28] Lei K, Chen Y, Wang J, Peng X, Yu L and Ding J 2017 Acta

Biomater. 55 396[29] Shiralizadeh S, Nasr-Isfahani H, Keivanloo A and Bakherad M

2016 RSC Adv. 6 110400[30] Shiralizadeh S, Nasr-Isfahani H, Keivanloo A, Bakherad M,

Yahyaei B and Pourali P 2018 J. Mater. Sci. 53 9986[31] Novoselov K S, Geim A K, Morozov S V, Jiang D, Zhang Y,

Dubonos S V et al 2004 Science 306 666[32] Dreyer D R, Todd A D and Bielawski C W 2014 Chem. Soc.

Rev. 43 5288[33] Park S and Ruoff R S 2009 Nat. Nanotechnol. 4 217[34] Geim A K 2009 Science 324 1530[35] Geim A K and Novoselov K S 2007 Nat. Mater. 6 183[36] Yang K, Feng L, Shi X and Liu Z 2013 Chem. Soc. Rev. 42

530[37] Narayanan T N, Gupta B K, Vithayathil S A, Aburto R R, Mani

S A, Taha-Tijerina J et al 2012 Adv. Mater. 24 2992[38] Jin Y, Wang J, Ke H, Wang S and Dai Z 2013 Biomaterials 34

4794[39] Shi S, Yang K, Hong H, Valdovinos H F, Nayak T R, Zhang Y

et al 2013 Biomaterials 34 3002[40] Khansary M A, Mellat M, Saadat S H, Fasihi-Ramandi M,

Kamali M and Taheri R A 2017 Chemosphere 168 91[41] Taheri R A, Rezayan A H, Rahimi F, Mohammadnejad J and

Kamali M 2016 Biosens. Bioelectron. 86 484[42] Azin E, Moghimi H and Taheri R A 2017Desalin. Water Treat.

94 222[43] Hajipour H, Hamishehkar H, Nazari Soltan Ahmad S,

Barghi S, Maroufi N F and Taheri R A 2018 Artif. CellsNanomed. Biotechnol. doi: https://doi.org/10.1080/21691401.2017.1423493