See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/341567241

Enhanced drug efficiency of doped ZnO-GO (graphene oxide)

nanocomposites, a new gateway in drug delivery systems (DDSs) Enhanced
drug efficiency of doped ZnO-GO (graphene oxide) na...

Article · January 2020

CITATIONS READS

0 21

7 authors, including:

Hassan Afzal Mohammad Ikram

Government College University, Lahore Aligarh Muslim University
5 PUBLICATIONS   33 CITATIONS    54 PUBLICATIONS   124 CITATIONS   

SEE PROFILE SEE PROFILE

Salamat Ali Muhammad Aqeel

Government College University, Lahore Solar Cell Applications Research Lab Government College University, Lahore
126 PUBLICATIONS   818 CITATIONS    21 PUBLICATIONS   161 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Flexible Supercapacitors View project

Comparative efficacy of Drug loading and release from various Metallic Nanoparticles View project

All content following this page was uploaded by Muhammad Aqeel on 22 May 2020.

The user has requested enhancement of the downloaded file.

Materials Research Express

PAPER • OPEN ACCESS

Enhanced drug efficiency of doped ZnO–GO (graphene oxide)

nanocomposites, a new gateway in drug delivery systems (DDSs)
To cite this article: H Afzal et al 2020 Mater. Res. Express 7 015405

View the article online for updates and enhancements.

This content was downloaded from IP address 111.68.103.110 on 08/01/2020 at 03:57

 Mater. Res. Express 7 (2020) 015405 https://doi.org/10.1088/2053-1591/ab61ae

PAPER

Enhanced drug efficiency of doped ZnO–GO (graphene oxide)

OPEN ACCESS
nanocomposites, a new gateway in drug delivery systems (DDSs)
RECEIVED
23 October 2019
H Afzal1,7, M Ikram1,7 , S Ali2, A Shahzadi3, M Aqeel1, A Haider4, M Imran5 and S Ali6
REVISED 1
29 November 2019
Solar Cell Applications Research Lab, Department of Physics, Government College University Lahore, 54000, Punjab, Pakistan
2
Department of Gynaecology & Obstetric (Unit–III), Jinnah Hospital, Lahore, 54000, Punjab, Pakistan
ACCEPTED FOR PUBLICATION 3
College of Pharmacy, University of the Punjab, Lahore, 54000, Pakistan
12 December 2019 4
Department of Clinical Medicine and Surgery, University of Veterinary and Animal Sciences Lahore, 54000, Punjab, Pakistan
PUBLISHED 5
State key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Centre for Soft Matter Science and Engineering,
6 January 2020
Beijing Engineering Center for Hierarchical Catalysts, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of
China
Original content from this 6
Department of Physics, Riphah Institute of Computing and Applied Sciences (RICAS), Riphah International University, 14 Ali Road,
work may be used under Lahore, Pakistan
the terms of the Creative 7
Commons Attribution 4.0
H Afzal and M Ikram are equal contributors
licence. E-mail: dr.muhammadikram@gcu.edu.pk
Any further distribution of
this work must maintain Keywords: zinc oxide, graphene, chemical deposition, drug delivery
attribution to the
author(s) and the title of
the work, journal citation
and DOI.
Abstract
Graphene oxide (GO) nanosheets were doped to zinc oxide (ZnO) nanoparticles using a facile
chemical deposition method. X-ray diffraction (XRD) confirmed the presence of hexagonal structure
and increased peaks broadening upon doping. Undoped and ZnO doped GO sheets showed
morphology like nanoparticles, nanorods and flakes were observed under transmission and field
emission electron microscopies respectively. An increase in absorption was observed in absorption
spectra upon doping recorded via UV-visible spectroscopy. The hydrogen bonding between
functional groups of GO and ZnO is responsible for limiting maximum drug loading efficiency. GO
doped ZnO has higher drug loading efficiency of about 89% compared to ZnO (82%) and this trend
reverse in drug releasing process. This study will provide an efficient design of the drug delivery system
for dissolution enhancement according to the required drug release.

1. Introduction

Cancer, a complicated disease with hundred different types involves abnormal cell growth. World health
organization (WHO) described cancer deaths statistics comprised of 5-years analysis and reported 14.1 million
newly diagnosed, 32.6 million existing patients and 8.2 million deaths by cancer worldwide in 2012 [1–4].
Cancer cure is a hard challenge for science and medical experts involving current methods as surgery,
radiotherapy, chemotherapy, immunotherapy and photodynamic therapy [5–10]. Chemotherapy involves
agents such as (doxorubicin, mitomycin, daunorubicin and capecitabine) distribution inside body providing
non-target tumor specificity resulting in adverse effects like alopecia, loss of digestive capacities, and
immunosuppression [11–14].
Targeted cancer therapy and drug delivery systems (DDSs) having capability to differentiate between
cancerous and healthy cells with minimum side effects are utilized to prevent non-target tumor specificity [15].
Drug delivery systems (DDSs) comprising of nanomedicine with nanocarriers permit drugs and medical
therapies to play role in more convenient, safe and efficient way [11]. Noble metal (Ag and Au) and metal oxide
nanoparticles (Fe3O4, NiO, CoO, ZnO and SnO2) are promising materials for drug delivery [16–18]. Among
these, zinc oxide (ZnO) nanoparticles involvement in cancer therapy has received much attention. Recently,
ZnO in various structures like nanorods, nanospheres and nanodiscs found non-toxic exhibiting antibacterial,
antitumor and photocatalytic activity has been used in DDSs. These structures are also biocompatible, cost

© 2020 The Author(s). Published by IOP Publishing Ltd

Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 1. (a) 2D and (b) 3D chemical structure of DOX.

effective and richness in structure can be considered as a potential candidate for drug delivery
application [19, 20].
Graphene based nanocomposites having novel physical applications in various field, used as transparent
conductive electrodes and is explored widely in biomedical [21–26] for drug loading and release with low
toxicity and high biocompatibility in DDS [27–29]. Among carbon nanostructures, Graphene oxide (GO) is
modern posing two-dimensional (2D) structure with one-atom thickness having four times large surface area
relative to other nanomaterials used. Aromatic drugs (doxorubicin, camptothecin and paclitaxel) can be loaded
to GO nanosheets with high capacity via π-π stacking and hydrophobic interactions. Furthermore, GO can be
prepared economical in large amounts compared to inorganic nanomaterials. GO functionality imparts specific
biological properties upon introduction with covalent and non-covalent surface coatings [30–34]. Both ZnO
and GO are biocompatible and can demonstrate success in diverse drug delivery applications. Our work relies on
analysis of GO/ZnO formation and its comparison with ZnO in anticancer drug loading and release at different
pH values.
In present study, GO was prepared using modified Hummers procedure and utilized to synthesis GO/ZnO
nanocomposite. These undoped and doped GO were applied on anti-cancer drug DOX (figure 1) to check its
drug loading and release capacity.

2. Experimental details

2.1. Materials
Graphite flakes, hydrogen peroxide-H2O2 (30%) and potassium permanganate-KMnO4 (99.5%) were
purchased from BDH (England). Hydrochloric acid (HCl) (37%) from Merk (USA) and sodium nitrate-NaNO3
(99.0%) from DUKSAN (South Korea) were used. Sulfuric acid-H2SO4 (99.99%) and dialysis tubing (2000
MWCO) were procured from Sigma-Aldrich (USA). Sodium hydroxide (NaOH), ethanol (C2H5OH) and zinc
chloride (ZnCl2) were obtained from Riedel-de Haën (Germany), AnalaR (USA) and Panreac Química (Spain),
respectively. Doxorubicin HCl (10 mg 5 ml−1) (DOX) was obtained from Fresenius Kabi (USA). All reagents
were of analytical standard and utilized as received.

2.2. Preparation of graphene oxide sheets

Modified Hummers method was used to obtain GO from refined graphite powder [35]. First of all, H2SO4 (24
ml) and NaNO3 (0.51 g) were mixed with graphite powder (0.5 g) under vigorous stirring for 30 min at 0 °C then,
KMnO4 (3 g) was added in solution at 10 °C and stirred for 3 h till 35 °C. Deionized water (DIW) was gradually
added and temperature maintained at 100 °C for 2 h. H2O2 (10 ml) was introduced into water containing
mixture. Subsequently, fabricated material was washed several times with HCl (0.1 M) aqueous solution to
remove metal ions. Finally, obtained product dried at 70 °C for 24 h using oven to achieve GO sheets.

2.3. Preparation of ZnO and GO/ZnO nanomaterial

Facile chemical deposition route was adopted to synthesize ZnO and GO/ZnO nanomaterials [36]. To prepare
GO/ZnO, GO sheets (0.1 g) added in DIW (40 ml) were kept under ultra-sonication for 30 min to disperse GO
sheets and sodium hydroxide (NaOH, 0.2 g) and zinc chloride (ZnCl2, 0.1364 g) were mixed in above GO sheets
solution. The solution was stirred at 90 °C for 6 h and then was cooled to room temperature. The cooled solution
was washed several times with ethanol and DIW to remove impurities. Refined product was obtained after

2
Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 2. Schematic diagram of ZnO and GO/ZnO synthesis process.

heating at 90 °C for 24 h to achieve GO/ZnO nanomaterial powder (figure 2). Same procedure was employed
without addition of GO to fabricate ZnO nanoparticles.

2.4. Drug loading

Conjugation of nanomaterial to DOX was attained by forming dilution of DOX with DIW (100 μg ml−1).
Subsequently, ZnO (10 mg) were dispersed in DIW (2 ml) separately and then mixed in 1 ml of DOX dilution
(100 μg ml−1). Samples placed in ultra-sonication for 20 min for proper conjugation of medicine with GO
nanomaterials. All samples were placed in dark spot at orbital shaker for 24 h and ultra-centrifugation was
carried out at 15,000 rpm afterward. Finally, supernatant from all samples was characterized using UV–vis
spectrophotometer at 480 nm absorbance to measure loading efficiency. Loading efficiency and capacity were
calculated by equations [17] using UV–vis spectrophotometer at 480 nm absorbance to measure loading
efficiency (figure 3).

% Loading Efficiency = [(DOXi - DOXf ) DOXi] ´ 100 (1)

Loading Capacity (mg mg-1) = [(DOX i - DOXf ) Drug carrier] (2)

Whereas, DOXi and DOXf are the initial amount (μg) of desired drug and unbound drug in supernatant,
respectively and Drugcarrier is total quantity (mg) of nanoparticles.

2.5. Drug release

For drug release, a standard curve was used to predict the concentration of DOX (figure 4(b)). The obtained
pallet after centrifugation containing DOX loaded on GO/ZnO nanomaterials was placed in daialysis tubing
after mixing with 3 ml buffer solution. Drug on loaded (GO/ZnO) nanomaterials start to release as dialysis
tubing suspended in 100 ml of buffer solution beaker. Drug release was checked for 24 h in which, 3 ml aliquots
were withdrawn each hour and analyzed through UV–vis spectrophotometer. Meanwhile, 3 ml fresh buffer was
added again in beaker to maintain sink condition (figure 4(a)). Two different pH values (3 and 11) were used to
analyze pH variation on drug-releasing properties. Drug Release percentage was calculated by the equation
below [37]:

Drug Release % = (Dt Do ) ´ 100 (3)

Whereas, Dt is the drug released by nanomaterials at given interval while Do is the total amount of drug loaded
on nanoparticles.

3
Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 3. Illustration of drug loading procedure.

Figure 4. (a) Release mechanism of DOX from study samples and (b) DOX standard curve.

2.6. Characterization
Nanomaterials were characterized via x-ray diffraction (XRD), UV–vis spectroscopy (UV–vis) and field
emission scanning electron microscopy (FE-SEM). For XRD, PANanlytical Xpert Highscore PRO was utilized
for crystallinity and phase detection for 2θ variation from 5°–70° with radiation source Cu Kα (λ∼0.154 nm).
Drug loading and release properties of nanohybrids (ZnO, GO/ZnO) DOX along with optical characteristics
were examined through UV–vis-Genesys 10S spectrophotometer. Information regarding surface morphology
and elemental composition were examined by JSM-6460LV FE-SEM using Cu-grid coupled with EDX
spectrometer.

3. Results and discussion

Representation of XRD patterns of GO, ZnO and GO/ZnO are indicated in figure 5. The Braggs diffraction
peaks from ZnO and GO doped ZnO samples, the observed planes are identical (100), (002), (101), (102), (110),
(103) and (112) at different diffraction angles 31.5°, 34.3°, 36.1°, 47.3°, 56.3°, 62.5° and 67.7° respectively [38].
The observed peaks indicates crystalline behavior with hexagonal structure (JCPDS 01-079-0208). It was

4
Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 5. XRD patterns of fabricated samples of GO, ZnO and GO/ZnO.

Figure 6. (a) FE-SEM image of GO, (b) HR-TEM nanograph of GO sheets and (c), (d) FE-SEM images of ZnO and GO/ZnO,
respectively.

observed that crystallinity of ZnO decreased upon GO with slight shift towards lower angles. The calculated
average crystallite sizes through Debye–Scherrer’ formula [39] are 33.56 nm (ZnO) and 18.41 nm (GO/ZnO). A
significant decrease in crystallite size was observed due to incorporation of GO in ZnO sample compared to
ZnO [38].
Morphological analysis of GO, ZnO and GO:ZnO, FE-SEM and HR-TEM was deployed to samples, the
observed structure and size are illustrated in in figure 6. FESEM layered structure of GO in figure 6(a) can be seen
but more visible in HR-TEM image as shown in figure 6(b). FESEM of ZnO is demostrating an integrated
structure consisting of nanorods and flakes figures 6(c), (d) [40]. The merging π-π stacking wrinkled GO sheets
with ZnO resulted slight conversion of nanorods to particles along with agglomeration of flakes present in ZnO
structure can be seen in figure 6(d).

5
Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 7. EDX spectra of (a) GO, (b) ZnO and (c) GO/ZnO.

Figure 8. (a) UV–vis spectra of GO, ZnO and GO/ZnO and (b) band gap energy.

The chemical composition of GO, ZnO and GO conjugated ZnO was investigated using EDX (figure 7). The
presence of O, C and Zn involvement in the product was confirmed by EDX analysis and observed ratios are
described in inset of figure (a)–(c). The peaks of O and Zn are manifested to ZnO while, C content ascribed to
GO nanosheets. Rest of the detected elemental peaks (K, Mn, Na) in the GO samples could be due to KMnO4,
NaOH were utilized during GO synthesis process. Cu coating of samples for FESEM analysis was found
responsible for Cu peak in desired material.
Absorption spectra of synthesized materials GO, ZnO and doped ZnO was collected between absorption and
wavelength which played vital role to monitor band gap energy probed via UV–vis spectrophotometer (figure 8).
GO showed absorption edge band around 230 nm representing (C=C) with shoulder peak in GO around ∼300
nm (C=O bonds) [41] and ZnO at 375 nm exhibits a characteristic absorption peak of wurzite hexagonal phase
of ZnO [42]. The absorption increased between 245–400 nm with GO doping and this increase in absorption
suggests about the bandgap variation of fabricated nanostructured. To attain energy bandgap from Tauc’s plot:
firstly, Beer–Lambert relation was used to calculate absorption coefficient (α), α=(2.303A)/d, here A presents
absorbance and d is path length of glass cuvette (10 mm) having colloidal solution. In next step, Tauc’s equation
(ahu = B (hu - Eg )n) is used to obtain energy bandgap. In this equation, B, h and υ are constant, Plank’s

6
Mater. Res. Express 7 (2020) 015405 H Afzal et al

Figure 9. (a) Drug loading profile of DOX into nanomaterials, (b) comparison of LC and LE for drug and (c), (d) release behavior of
DOX from prepared samples at different pH.

constant and frequency of photon respectively, Eg is bandgap energy and n illustrates type of optical transition.
Hence n=1/2 is put in present case attributed to direct bandgap of prepared material and Tauc’s plot (ahu 2
versus hυ) is depicted in (figure 8(b)). Finally, bandgap of prepared nanomaterials were calculated by Tauc
transformation spectra and extrapolation used on X-axis. Energy bandgap of pure ZnO found 3.28 eV [43] and
with GO bandgap energy increased around 3.32 eV.
Drug loading efficiency (LE) and loading capacity (LC) of ZnO and GO/ZnO were evaluated using
equations (1) and (2) and UV–vis absorption spectra (DOX loading spectra) as displayed in figure 9(a). A
significant increase in LE of GO:ZnO was observed which could be due to existence probability of hydrogen
bonding between –OH and −COOH groups of GO and –OH and −NH2 groups of DOX [44]. LE calculated for
ZnO and GO/ZnO was found 82 and 89% respectively. On the other hand, LC of control sample was
∼6.30 μg mg−1 and doped ZnO has 7.47 μg mg−1 which is low in comparison to LE (figure 9(b)) as we used very
small weight ratio of DOX compared to nanoparticles. Drug release profile analyzed in different media is
demonstrated in figures 9(c), (d). Cumulative drug release % for ZnO-DOX was observed highest (100%) in
basic (∼pH=11) along with lowest (46%) in acidic solution (∼pH=3) and same trend found for GO/ZnO-
DOX due to partial dissociation of the hydrogen-bonding interaction under acid and basic environments.
Mostly, ZnO exhibited enhanced drug releasing efficiency in both media but basic media was found more
suitable.

4. Conclusion

In present work, GO was fabricated by modified Hummers method and successfully incorporated in synthesized
ZnO nanoparticles (∼18.41 nm average crystallite size) using facile chemical deposition route. XRD pattern
revealed that ZnO hexagonal lattice and decrease in crystallinity was found upon doping. The merging π-π
stacking wrinkled GO sheets with ZnO lattice resulted conversion of nanorods to flakes examined by FE-SEM.
The calculated bandgap of doped ZnO is found 3.32 eV relative to ZnO (2.28 eV) is attributed to increase in
absorption upon doping. Drug LE increased with doped GO content (89%) and ZnO possessed (82%)

7
Mater. Res. Express 7 (2020) 015405 H Afzal et al

corresponding to hydrogen bonding between GO and ZnO. The release rate showed reverse behaviour from LE
as ZnO attained high rate about 46% (∼pH=3 ) and 100% (∼pH=11) in comparative estimate to GO/ZnO
having 35% (∼pH=3) and 41% (∼pH=11). This drug loading and releasing approach and design would be
benificial and provide a new gateway with dissolution enhancement in drug delivery systems.

Acknowledgments

Authors are grateful to higher education commission (HEC), Pakistan for financial support through start
research group (SRGP) project number 21-1669.

Conflict of interest

Authors confirm that this manuscript has no conflict of interest.

ORCID iDs

M Ikram https://orcid.org/0000-0001-7741-789X

References
[1] Chowdhury S, Yusof F, Salim W W, Sulaiman N and Faruck M O 2016 An overview of drug delivery vehicles for cancer treatment:
nanocarriers and nanoparticles including photovoltaic nanoparticles J. Photochem. Photobiol., B 164 151–9
[2] Bowen C, Resnick S and Crane R 2008 Essential Windows Communication Foundation: for. Net Framework 3.5. (Reading, MA: Addison-
Wesley)
[3] Ferlay J GLOBOCAN 2008, cancer incidence and mortality worldwide: IARC CancerBase No. 10 http://globocan.iarc. fr. 2010
[4] Acs Z J and Szerb L 2007 Entrepreneurship, economic growth and public policy Small Business Economics. 28 109–22.
[5] Deng Y and Zhang H 2013 The synergistic effect and mechanism of doxorubicin-ZnO nanocomplexes as a multimodal agent
integrating diverse anticancer therapeutics Int. J. Nanomed. 8 1835
[6] CAO H, Phan H and Yang L X 2012 Improved chemotherapy for hepatocellular carcinoma Anticancer Res. 32 1379–86
[7] Bae B C and Na K 2010 Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for
photodynamic therapy Biomaterials 31 6325–35.
[8] Guo H, Qian H, Idris N M and Zhang Y 2010 Singlet oxygen-induced apoptosis of cancer cells using upconversion fluorescent
nanoparticles as a carrier of photosensitizer Nanomed. Nanotechnol. Biol. Med. 6 486–95.
[9] He X, Wu X, Wang K, Shi B and Hai L 2009 Methylene blue-encapsulated phosphonate-terminated silica nanoparticles for
simultaneous in vivo imaging and photodynamic therapy Biomaterials 30 5601–9
[10] Khdair A, Gerard B, Handa H, Mao G, Shekhar M P and Panyam J 2008 Surfactant− polymer nanoparticles enhance the effectiveness
of anticancer photodynamic therapy Mol. Pharmaceutics 5 795–807
[11] Fan J, Wang S, Sun W, Guo S, Kang Y, Du J and Peng X 2018 Anticancer drug delivery systems based on inorganic nanocarriers with
fluorescent tracers AlChE J. 64 835–59
[12] Juillerat‐Jeanneret L and Schmitt F 2007 Chemical modification of therapeutic drugs or drug vector systems to achieve targeted
therapy: looking for the grail Medicinal Research Reviews. 27 574–90
[13] Freiberg S and Zhu X X 2004 Polymer microspheres for controlled drug release Int. J. Pharm. 282 1–8
[14] He Q and Shi J 2014 MSN anti‐cancer nanomedicines: chemotherapy enhancement, overcoming of drug resistance, and metastasis
inhibition Adv. Mater. 26 391–411
[15] Bahramia B, Hojjat-Farsangic M, Mohammadi H, Anvarig E, Ghalamfarsah G, Yousefi M and Jadidi-Niaragh F 2017 Nanoparticles
and targeted drug delivery in cancer therapy Immunology Letters. 190 64–83
[16] Javed K R, Ahmad M, Ali S, Butt M Z, Nafees M, Butt A R, Nadeem M and Shahid A 2015 Comparison of doxorubicin anticancer drug
loading on different metal oxide nanoparticles Medicine. 94 1–6
[17] Naz M, Nasiri N, Ikram M, Nafees M, Qureshi M Z, Ali S and Tricoli A 2017 Eco-friendly biosynthesis, anticancer drug loading and
cytotoxic effect of capped Ag-nanoparticles against breast cancer Applied Nanoscience. 7 793–802
[18] Lee C S, Kim H, Yu J, Yu S H, Ban S, Oh S, Jeong D, Im J, Baek M J and Kim T H 2017 Doxorubicin-loaded oligonucleotide conjugated
gold nanoparticles: a promising in vivo drug delivery system for colorectal cancer therapy Eur. J. Med. Chem. 142 416–23.
[19] Liu J, Ma X, Jin S, Xue X, Zhang C, Wei T, Guo W and Liang X J 2016 Zinc oxide nanoparticles as adjuvant to facilitate doxorubicin
intracellular accumulation and visualize pH-responsive release for overcoming drug resistance Mol. Pharmaceutics 13 1723–30
[20] Huang X, Zheng X, Xu Z and Yi C 2017 Zno-based nanocarriers for drug delivery application: From passive to smart strategies Int. J.
Pharm. 534 190–4
[21] Tang L Y, Wang Y C, Li Y, Du J Z and Wang J 2009 Shell-detachable micelles based on disulfide-linked block copolymer as potential
carrier for intracellular drug delivery Bioconjugate Chem. 20 1095–9
[22] Liu Z, Sun X, Nakayama-Ratchford N and Dai H 2007 Supramolecular chemistry on water-soluble carbon nanotubes for drug loading
and delivery ACS Nano. 1 50–6
[23] Santra S, Kaittanis C, Grimm J and Perez J M 2009 Drug/dye‐loaded, multifunctional iron oxide nanoparticles for combined targeted
cancer therapy and dual optical/magnetic resonance imaging Small. 5 1862–8
[24] Guo R, Li R, Li X, Zhang L, Jiang X and Liu B 2009 Dual‐functional alginic acid hybrid nanospheres for cell imaging and drug delivery
Small. 5 709–17
[25] Purushotham S and Ramanujan R V 2010 Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy Acta
Biomater. 6 502–10

8
 Mater. Res. Express 7 (2020) 015405 H Afzal et al

[26] Yokoyama M, Fukushima S, Uehara R, Okamoto K, Kataoka K, Sakurai Y and Okano T 1998 Characterization of physical entrapment
and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor J. Controlled Release
50 79–92
[27] Zhang L, Xia J, Zhao Q, Liu L and Zhang Z 2010 Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery
of mixed anticancer drugs Small. 6 537–44
[28] Burger K N, Staffhorst R W, de Vijlder H C, Velinova M J, Bomans P H, Frederik P M and de Kruijff B 2002 Nanocapsules: lipid-coated
aggregates of cisplatin with high cytotoxicity Nat. Med. 8 81
[29] Wei W, Ma G H, Hu G, Yu D, Mcleish T, Su Z G and Shen Z Y 2008 Preparation of hierarchical hollow CaCO3 particles and the
application as anticancer drug carrier JACS 130 15808–10
[30] Hashemi M, Yadegari A, Yazdanpanah G, Omidi M, Jabbehdari S, Haghiralsadat F, Yazdian F and Tayebi L 2017 Normalization of
doxorubicin release from graphene oxide: new approach for optimization of effective parameters on drug loading Biotechnol. Appl.
Biochem. 64 433–42
[31] Yadegari A, Omidi M, Choolaei M, Haghiralsadat F and Yazdian F 2014 Micro-newton detection by using graphene-paper force sensor
Procedia Engineering. 87 967–70.
[32] Yang K, Feng L and Liu Z 2015 The advancing uses of nano-graphene in drug delivery Expert opinion on drug delivery. 12 601–12
[33] Liao K H, Lin Y S, Macosko C W and Haynes C L 2011 Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin
fibroblasts ACS applied Materials & Interfaces. 3 2607–15
[34] Byun J 2015 Emerging frontiers of graphene in biomedicine J. Microbiol. Biotechnol. 25 145–51
[35] Aqeel M, Anjum S, Imran M, Ikram M, Majeed H, Naz M, Ali S and Ahmad M A 2019 TiO2@ RGO (reduced graphene oxide) doped
nanoparticles demonstrated improved photocatalytic activity Mater. Res. Express 6 086215
[36] Li B, Liu T, Wang Y and Wang Z 2012 ZnO/graphene-oxide nanocomposite with remarkably enhanced visible-light-driven
photocatalytic performance J. Colloid Interface Sci. 377 114–21
[37] Prasad D 2017 Nanoparticulate drug delivery systems, in vitro drug release test methods Int J Pharm Bio Sci. 8 103–9
[38] Durmus Z, Kurt B Z and Durmus A 2019 Synthesis and characterization of graphene oxide/zinc oxide (GO/ZnO) nanocomposite and
its utilization for photocatalytic degradation of basic fuchsin dye ChemistrySelect. 4 271–8
[39] Langford J I and Wilson A J 1978 Scherrer after sixty years: a survey and some new results in the determination of crystallite size J. Appl.
Crystallogr. 11 102–13.
[40] Logamani P, Rajeswari R and Poongodi G 2017 Enhanced photocatalytic activity of rare earth metal (Nd and Gd) doped ZnO
nanostructures2 Mechanics, Materials Science & Engineering Journal. 9
[41] Rabchinskii M K et al 2016 Nanoscale perforation of graphene oxide during photoreduction process in the argon atmosphere The
Journal of Physical Chemistry C. 120 28261–9
[42] Estrada-Urbina J, Cruz-Alonso A, Santander-González M, Méndez-Albores A and Vázquez-Durán A 2018 Nanoscale zinc oxide
particles for improving the physiological and sanitary quality of a Mexican landrace of red maize Nanomaterials. 8 247
[43] Rauf M A, Owais M, Rajpoot R, Ahmad F, Khan N and Zubair S 2017 Biomimetically synthesized ZnO nanoparticles attain potent
antibacterial activity against less susceptible S. aureus skin infection in experimental animals RSC Adv. 7 36361–73.
[44] Yang X, Zhang X, Liu Z, Ma Y, Huang Y and Chen Y 2008 High-efficiency loading and controlled release of doxorubicin hydrochloride
on graphene oxide The Journal of Physical Chemistry C. 112 17554–8

View publication stats