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Current Drug Targets, 2017, 18, 724-733

REVIEW ARTICLE
ISSN: 1389-4501
eISSN: 1873-5592

Graphene: A Comprehensive Review Impact

Factor:
3.029

BENTHAM
SCIENCE

Aditya D. Ghuge*, Abhay R. Shirode and Vilasrao J. Kadam

Bharati Vidyapeeth’s College of Pharmacy, CBD Belapur, Navi Mumbai, Maharashtra, 400614, India

ARTICLE HISTORY
Received: November 05, 2015
Revised: March 11, 2016
Accepted: June 30, 2016
DOI:
10.2174/138945011766616070902
3425
Abstract: Graphene, a one-atom thick, two-dimensional sheets of sp2hybridized carbon atoms packed
in a hexagonal lattice with a Caron-Carbon distance of about 0.142 nm. Its extended honeycomb net-
work forms the basic building block of other important allotropes; it can be stacked to form 3-D-
graphite, rolled to form 1-D-nanotubes and wrapped to form 0-D-fullerenes. Long-range π conjugation
in graphene results in its extraordinary thermal, mechanical and electrical properties, which have been
the interest of many theoretical studies and recently became an exciting area for scientists. Graphene is
impermeable to gas and liquids, has excellent thermal conductivity and higher current density in com-
parison to other most effective materials. All of its exceptional properties have opened up new avenues
for the use of graphene in nano-devices and nano-systems, which initiated its prominent use as a mate-
rial for drug targeting. In addition, several fabrication techniques are outlined, starting from the me-
chanical exfoliation of high-quality graphene to the direct growth on silicon carbide or metal substrates
and from the chemical routes utilizing graphene oxide to the newly developed approach at the molecular
level. By this article reviewers intend to emphasize on unique properties, fabrication techniques and up-
dated applications of graphene. In addition, we discuss about the potential of graphene in drug targeting
in fields of nanotechnology, biomedical engineering and technology and its use for innovations in vari-
ous fields such as electronics and photonics.

Keywords: Drug targeting, graphene, honeycomb lattice, nanomaterial, one atom thickness, two-dimensional sheet.

1. INTRODUCTION 1947: P.R Wallace published a paper regarding band struc-

ture of ‘Graphite’ and the possibility of obtaining 2-D crys-
Till date many review articles regarding properties, fabri-
Current Drug Targets

tals of ‘Graphene’ from 3-D ‘Graphite’.

cation methods, applications in various fields of graphene are
published, but they rarely had updated information regarding
graphene. This article on the other hand contains complete
and updated information of graphene, which will be very
useful for the readers.
Graphene, the designation emanates from two words
‘graphite’ and ‘ene’. It is a one atom thick, two-dimensional
sheet of sp2-hybridized carbon. Its unique honeycomb struc-
ture is the basis for fabrication of many carbon allotropes
such as to fabricate 3-D graphite, 1-D nanotubes, and 0-D
fullerenes. Its excellent electrical, thermal and mechanical
properties are due to the long-range π -conjugation in gra-
phene, which are becoming an exciting area of research for
scientists [1].
The discovery of graphene in chronological order can be
outlined as follows:-
1930:Landau and Peierls thermodynamically reported the
possibility of obtaining 2-D Crystals from 3-D Crystals.
*Address correspondence to this author at the Bharati Vidyapeeth’s College
of Pharmacy, CBD Belapur, Navi Mumbai, Maharashtra, 400614, India;
Tel: +91 (22) 27571122; E-mail: adityadghuge18@gmail.com
1956: J.W. McClure gave the wave equation for excitations
in ‘Graphite’.
1984: G.W. Semenoff published a paper predicting unique
properties of ‘Graphene’.
2004: Andre Geim and Konstantin Novoselov managed to
obtain 2-D ‘Graphene’ flakes and bulk 3-D ‘Graphite’.
2010: Andre Geim and Konstantin Novoselov were award-
ed a Noble prize in physics for discovery and work on ‘Gra-
phene’.
The mechanical exfoliation method utilized by the ‘Man-
chester university’ research team was successful in isolating
the two-dimensional graphene from three-dimensional
graphite, which resulted in single to few-layer. The single
layers can be obtained by etching away the substrate, which
are attached to substrate by Van der Wall forces. Large
amount of new fascinating facts of physics were openly ac-
cessed due to the single layer experimental isolation of gra-
phene. This led to probing of intrinsic properties of graphene
by scientists. Following studies revealed graphene’s quantum
Hall Effect, extremely high electron mobility and many other
interesting facts. Due to the extraordinary properties pos-

1873-5592/17 $58.00+.00 © 2017 Bentham Science Publishers

Graphene: A Comprehensive Review
sessed by graphene, it unlocked many new avenues for its
use in nano-devices and nano-systems, which initiated its
prominent use as a material for drug targeting [2]. These
include current nano-systems, which are prominently used
for targeted deliveries such as gene-targeted delivery, drug
delivery, tissue targeted delivery. Recently, graphene has
been used in cancer-targeted therapies. Its use and applica-
tions also involve future nano-devices such as radio fre-
quency logic contrivances, thermally and electrically rein-
forced composite, sensors and electrodes for exhibition and
solar cells. Until now, mechanical exfoliation, the original
method for graphene preparation has given the highest qual-
ity flakes, but lacked in high throughput and high-yield. Due
to the difficulties in scalable production of high quality
flakes, wide implementation of graphene has not occurred
yet though there is intense scientific interest [3, 4].
The difficult task is to make double fold layer because
the number of layers and the overall quality of the crystal
lattice determines the final performance of graphene flakes.
Exfoliation of a single sheet is possible only when Van der
Waals forces are overcome between first and second layer
without any disruption to subsequent layer. Therefore, vari-
ous possible alternatives to obtain single layer flakes are
endeavored. Few of them have shown promising ways [5, 6].
1.1. Structure and Morphology of Graphene
1.1.1. Electronic Structure of Graphene
The electronic structure can be seen from (Fig. 1), which
constitutes of first brillouin zone (brown), second brillouin
zone (light pink), six corners of first brillouin zone called
‘Dirac points’ (also referred as K points). These Dirac Points
are the transition between the valence band and the conduc-
tion band [7-9].
Fig. (1). Electronic Structure of Graphene, First Brillouin Zone
(Brown), Second Brillouin Zone (Light Pink). (For interpretation
of the references to color in this figure legend, the reader is re-
ferred to the web version of this paper.)
(Fig. 2) part (a), Detailed 3-Dimensional structure of
Graphene shows the six dirac points which can be divided
into two in-equivalent sets of three (K and K'), represented
Current Drug Targets, 2017, Vol. 18, No. 6 725
by the black and white dots. The points within each set are
all equivalent because they can reach each other by recipro-
cal lattice vectors. (Fig. 2) part (b) shows that the dispersion
relation of the K points looks like the energy spectrum of
massless dirac particles [10, 11].
1.1.2. Morphology of Graphene
The graphene honeycomb lattice consists of two equiva-
lent sub-lattices of carbon atoms, which are bonded together
with σ bonds. Each carbon atom in the lattice has one orbital,
which results in a delocalized network of electrons’. The
Monte Carlo simulation and transmission electron micros-
copy (TEM) studies have revealed the intrinsic ripples of
suspended graphene. The microscopic corrugations showed
lateral dimensions of 8-10 nm and a height displacement of
about 0.7- 1 nm. Micrometer range fluctuations in height of
graphene flakes deposited on silicon dioxide were observed
using scanning tunneling microscopy (STM) [12, 13].
2. PROPERTIES OF GRAPHENE
The important properties of graphene which are famously
tagged as ‘Supernatural’ because of their superiority over
many existing materials are given as below:
2.1. Electronic Properties
Due to its unique electronic properties, graphene finds
application in several semiconductor electronic devices such
as high frequency transistors and logic transistors, which are
listed below:
2.1.1. Conductivity ( σ )
The sheet conductivity of a 2D material is given by
.
The bulk conductivity using the layer thickness for gra-
pheneis about 1x106 Ω-1cm-1, it is higher than the conductiv-
ity of copper which is about0.60x106 Ω-1 cm-1 [14].
2.1.2. Electron Mobility (µ)
It is theoretically limited to [μ=200,000 cm2 V-1 s-1] by
acoustic phonons at a carrier density of n=1012 cm-2 [15].
2.1.3. Resistivity (ρ)
The 2D sheet resistivity, also called the resistance per
square, is 1.5 X 10-6 ῼ m [16].
2.2. Optical Properties
Owing to its excellent transmittance property, graphene
now days is used in smart optical devices as well as in solar
cells. The optical properties of graphene are outlined as be-
low:
2.2.1. Absorbance (A)
Monolayer graphene absorbs πα ≈ 2.3% of white light,
where α is the fine-structure constant’. Its optical electronics
absorb <10% white light.
2.2.2. %Transmittance (%T)
Monolayer graphene transmits 97.7 % of white light
[17].
726 Current Drug Targets, 2017, Vol. 18, No. 6
Figure 2 (a)
Fig. (2). Detailed 3-Dimensional Structure of Graphene showing, (a):- Shows the six Dirac points which can be divided into to two in-
equivalent sets of three (K and K'), represented by the black and white dots. (b):- Shows that the dispersion relation close to the K points
looks like the energy spectrum of massless Dirac particles.
2.3. Thermal Properties
Graphene due to its thermal conductivity has emerged as
a potential replacement for diamond in several thermal de-
vices. Thermal conductivity of graphene is therefore an im-
portant thermal property, which is highlighted below:
2.3.1. Thermal Conductivity
The thermal conductivity of graphene is dominated by
phonons. It has been measured to be approximately 5000
Wm−1K−1, whereas diamond (the best thermal conductive
material) at room temperature has a thermal conductivity of
1000 Wm−1K−1’. Therefore graphene is approximately 10
times better conductor of heat than diamond [18].
2.4. Mechanical Properties
Graphene is widely known for its mechanical properties
which are detailed below:
2.4.1. Bond Length
It is about 0.142 nm, which is responsible for its very
strong intermolecular bonding. It has inter-planar distance of
about 0.332 nm which contributes to it strength [19].
2.4.2. Strength
It is strongest material ever discovered because it has ul-
timate tensile strength of 130 Gpa compared to 400 Mpa for
structural steel. Hence, it is about 200 times stronger than
structural steel.
Graphene has high Young’s modulus of about 15 x 108
psi, which effectively contributes to its enormous strength.
2.4.3. Flexibility
Single sheet of graphene can cover a whole football field
while weighing less than 1 gram.
Graphene is very light in terms of its weight as it weighs
about 0.77 mg/m2, which is 1000 times lighter than paper
[20, 21].
Ghuge et al.
Figure 2 (b)
A quick overview of graphene’s properties is presented in
(Table 1).
3. FABRICATION TECHNIQUES FOR GRAPHENE
Fundamentally, there are two distinct ways to fabricate
graphene. One is Detachment of graphene layer from exist-
ing graphite crystal, called ‘exfoliation method’ and second
indirect approach is to grow graphene layer on substrate sur-
face. K. Novoselov and A. Geim in 2004 reported the prepa-
ration of graphene by exfoliation utilizing simple adhesion
tape. Fabrication methods are as follows.
3.1. Direct Approach Methods
3.1.1. The Scotch Tape Method
This micromechanical exfoliation method of graphene
preparation is about detachment of layers from a graphite
crystals using adhesive tape. In this method crystal block of
graphite is taken and adhesive tape is stuck on to it. Gra-
phene layers remains on the tape after repeated peeling
which results into various flakes of few layer graphene. Then
attachment of tape to substrate (for example, acetone) takes
place in order to detach the tape and the glue solved. The
flakes obtained differ considerably in size and thickness of
single layer of graphene, depending on the preparation of
used wafer. Graphene has absorption of 2%; nevertheless, it
is possible to see it under a light microscope on silicon diox-
ide or silicon due to interference effects. Larger amount of
graphene is difficult to obtain by this method though it lacks
controllability in shape and size of graphene layer, the qual-
ity of graphene obtained is excellent [22].
3.1.2. Dispersion of Graphite
Graphene preparation can be done in liquid-phase disper-
sion. In this method liquid phase dispersion of graphite is
prepared. The solution is then sonicated in an ultrasound
bath for several hundred hours with voltage applied. After
dispersion, in order to dispose the thicker flakes, the solution
has to be centrifuged. This allows upscaling the production
Graphene: A Comprehensive Review
Table 1. Comparison of Graphene’s supernatural properties with best known existing materials [14-21].
Properties Property Possessed by Best Known Existing Materials
Electronic Properties
• Electron Mobility Silicon (1.4 X 103 cm2v-1s-1)
• ῤ)
Resistivity (ῤ Silver (1.59 X 10-6 ῼ m) at R.T.
• Current Capacity Copper (0.60 x108 Ω-1 cm-1).
• Modifiable Electronic Properties ---
Optical (%Transmittance) Silver nanowires (90%)
Thermal conductivity Diamond (1000 W mK-1)
Mechanical strength Steel:
Intrinsic tensile strength: 200 GPa
Young’s Modulus: 29,000,000 psi
in order to obtain a much higher amount of graphene. The
easiest approach for dispersion of graphene is dispersing it in
organic solvent with nearly the same surface energy as
graphite. This reduces energy barrier, which has to be over-
come to detach a graphene layer from the crystal. Graphene
flakes obtained by this method is of very high quality. The
size of graphene flakes obtained is still very small and it is
not controllable.
3.1.3. Graphite Oxide Exfoliation
Graphite oxide exfoliation is done by dispersing graphite
oxide in water by sonication or stirring. Hydrophilic nature of
graphite oxide is due to presence of several functional groups
like epoxide, hydroxyl etc. In this method graphite powder is
mixed with strong acid (for example H2SO4) and strong oxi-
diser (for example perchloric acid) in water, which produces
graphene oxide. Then this graphene oxide is kept in a furnace
or microwave at about 1000oC to give exfoliated graphene
oxide. Furthermore, the addition of reducing agent (for exam-
ple oxalic acid) gives reduced graphene oxide. During this
reaction, its hard to remove all the oxygen molecules from
graphene oxide and therefore some traces of oxygen still re-
mains in final product i.e. graphene. Therefore, due to com-
plexicity of conversion of graphene oxide to graphene, gra-
phene oxide is considered to be the desired product.
The complexity of this method is high due to the produc-
tion of graphene oxide first, which requires the use of several
chemicals. Also the obtained graphene oxide has to be re-
duced to graphene afterwards using thermal treatments or
chemical treatments again. Reduced form of graphene oxide
is of bad quality compared to graphene obtained by other
methods [23].
3.1.4. Substrate Preparation
Substrate preparation involves different methods in order
to use the dispersed graphene in a non liquid phase.
Current Drug Targets, 2017, Vol. 18, No. 6 727
Graphene’s Supernatural Properties
2.5 X 105 cm2 v-1s-1
(1.5 X 10-6 ῼ m) at R.T.
1 x108 Ω-1cm-1 .
Can be modified for Conductor, Semiconductor
and even Insulator.
>97.7 %
4800-5000 W mK-1
Intrinsic tensile strength:
1000 GPa
Young’s Modulus: 15,00,000,000 psi
The prepared dispersion is sucked through a membrane
via vacuum filtration using a vacuum pump. Hence graphene
flakes deposits as filtration cake of graphene paper.
Deposition of graphene on a surface can be done by sim-
ple drop casting where drop of dispersion is placed on top of
the substrate. After solvents have evaporated, the graphene
flakes remains on the surface. To achieve homogeneous
coating the sample is rotated utilizing the spin coating
method for dispersing the solution with the help of centrifu-
gation, with spray coating the dispersed solution is sprayed
on the sample, which allows the preparation of more sizably
voluminous areas. This method has a high throughput and
produces high quality graphene [24].
3.2. Indirect Approach (Growth on Surfaces) Methods
This method is a consummately different approach to ob-
tain graphene, where graphene has to grow directly on a sur-
face consequently, the size of the layers obtained is inde-
pendent on the initial graphite crystal. The development sof
graphene sheet can occur by two different ways. Either the
carbon already exists in the surface or it has to be integrated
by chemical vapor deposition (CVD).
3.2.1. Epitaxial Growth
Graphene can be prepared by use of substrate i.e. epi-
taxial growth method. It can be done using following two
approaches.
3.2.1.1. Using Silicon Carbide (SiC) Crystals
Graphene can be prepared by simply heating and cooling
down an silicon carbide (SiC) crystal. Single or bilayer gra-
phene forms on the silicon surface of the crystals, whereas
few layers grows on the carbon surface of the silicon carbide
crystal. The result depends highly on the process parameters
like temperature, pressure and heating rate. In fact, if the
temperature and pressure are not controlled, it may result
728 Current Drug Targets, 2017, Vol. 18, No. 6
into nanotubes as a final product instead of graphene. The
growth of graphene at several locations on the crystals simul-
taneously and these graphene islands grows together. There-
fore, the graphene is not perfectly homogenous due to de-
fects or grain boundaries, its quality therefore is not as good
as that of exfoliated graphene, except the graphene would be
grown on a perfect single crystal.
3.2.1.2. Using Nickel Diffusion Method
The Nickel (Ni) surface has lattice structure similar to
that of graphene with similarity of lattice constant of about
98.7%. This method is similar to that of Nickel diffusion
method, in which a thin Ni layer is evaporated onto a SiC
crystal. Upon heating the carbon diffuses into through Ni
layer and forms a graphene or graphite layer on the surface,
depending on heating rate. Hence the graphene produced is
easier to detach from the SiC crystal than the growth on sur-
face without Ni. It is a perferred method over epitaxial
growth using SiC crystals [25].
3.2.2. Chemical Vapour Deposition
Chemical Vapor Deposition is prominent process where a
substrate is exposed to gas containing various functional
groups like amine, methane, hydrogen etc. In order to grow a
thin film these compounds decompose, whereas the byprod-
ucts evaporate. There are lots of different ways to achieve
this, example; by heating it with filament or plasma. Gra-
phene can be grown by exposing the nickel film to a gas
mixture of hydrogen, methane, argon at temperature about
1000οC.
The methane decomposes on the surface, so that the hy-
drogen evaporates. The carbon diffuses into the nickel. After
cooling down in an argon atmosphere, a graphene layer grows
on the surface. Hence, the average number of layers obtained
depends on the Ni thickness and can be controlled using ap-
propriate thickness of Ni. Furthermore, the shape of the gra-
phene can also be controlled by patterning of the Ni layer.
These graphene layers can be transferred via polymer support,
which will be attached onto the top of the graphene. After
etching the nickel, the graphene can be stamped onto the re-
quired substrate and the polymer support gets peeled off or
etched away. Using this method several layer of graphene can
be stamped on each other to decrease the resistance.
Chemical vapour deposition is most preferred method
due to several reasons like, best quality of graphene is ob-
tained, single and multiple layers are obtained, its controlla-
bility and cost effectiveness [26].
Comparison of different methods of fabrication is given
in (Table 2).
From the comparison table, we can conclude that chemi-
cal method is the most economical and best method for gra-
phene fabrication. Recent studies showed that chemical syn-
thesis followed by modified hammers method gives best
quality of graphene.
4. APPLICATIONS
4.1. Pharmaceutical and Biomedical Applications
Applying the nanotechnology basics to the principles of
biology provides a valuable route for further miniaturization
Ghuge et al.
and improvement for performance of artificial devices. ‘The
synergistic future of nano graphene and biotechnology holds
great promise for its applications in field like gene and drug
delivery, tissue engineering and cancer therapy’ [27].
4.1.1. Targeted Gene Delivery
Gene therapy is a powerful too, for treatment of various
diseases, both in born and aquired by producing bioactive
agents or blocking abnormal functions of the cells such as
genetic disorder or uncontrollable proliferation of cells. One
of the main issue in this area is the development of non viral
gene delivery vector or carriers with high efficiency of gene
transfection, which usually involves cationic polymers.
Liu et al. and Chen et al. observed that polythyen-
imine(PEI) used during transfection, when grafted to other
system decreases the transfection efficiency, but PEI modi-
fied graphene oxide proved to be a most promising candidate
for efficient gene delivery [28]. Kim et al. developed a gra-
phene oxide based efficient hybrid gene delivery carrier
through the installation of low molecular weight branched
plyethyenimine(BPEI), a cationic polymer, which has been
widely used as an efficient non viral gene delivery vector
[29].
4.1.2. Targeted Drug Delivery
The high surface area (2630 m2/g) and sp2 hybridized
carbon area are the biggest advantages of graphene over
other nano-materials that make it best carrier for drug load-
ing on both sides of single layer carbon sheet. There is a
need of interest in developing graphene for drug loading and
delivery because of strong interactions existing between hy-
drophobic drugs as well as aromatic regions of graphene
sheets [30].
Liu et al. functionalized nano graphene oxide a novel
graphitic material with branched polyethylene glycol to ob-
tain a (nanoscale graphene oxide) nGO-PEG (polyethylene
glycol) conjugate and use them for attaching hydrophobic
aromatic molecules like camptothecin analogue. In a study
conducted by sundar and prajapati have mentioned carbon
nanotube and graphene as an excellent therapeutics agent for
biomedical application. These nanoparticle are surface func-
tionalized with specific biomolecule based drug delivery had
driven a new direction for modulating the pharmacokinetics,
pharmacodynamics, biorecognisation and for increasing the
efficacy of targeted drugs. These new strategies would
minimize the drug degradation and increase the drug avail-
ability. Ran et al. reported the delivery of drug ibuprofen by
using a chitosan grafted and controlled its release by adjust-
ment of pH value.
Wen and his co-workers pointed out that incorporation of
PEG shell possesses a significant diffusion barrier that ad-
versely affects the release of loaded drug and therefore, em-
ployed a redox responsive PEG detachment mechanism. Ta-
hara et al. exploited the availability of large quantities of
single-walled carbon nanohorns (SWNHs) cytotoxicity and
the immunological responses induced by the abundant up-
take level in RAW 264.7 murine macrophages that resulted
in apoptosis and cell death [31]. Rana et al. reported the de-
livery of drug ibuprofen by using a chitosan grafted GO and
controlled its release by adjustment of pH values [32].
Graphene: A Comprehensive Review Current Drug Targets, 2017, Vol. 18, No. 6 729

Table 2. Comparison of different fabrication methods of Graphene [22-26].

Electronic Cost Number of Throughput Nature of Size of Compatibility Precursor

Quality of Layers Produced Layers With Chip
Layers Graphene Fabrication
Process

Mechanical exfolia- High Low Single and Low High Quality 10 µm No Graphite
tion multiple
(Scotch-tape
method)

Liquid suspension Low Low Single and High Chemically 100 No Graphite
graphene oxide multiple modified - oxide
followed by chemi- 1000
cal reduction Nm

Liquid-phase exfo- High High Single and High High Quality Very No Graphite
liation multiple small
(Substrate prepara- fragment
tion)

Epitaxial growth by High High Single and Low High Quality >50µm Yes Silicon
thermal desorption multiple carbide
of silicon atoms
from silicon-carbide
surface

Epitaxial growth by High Low Single and Low Chemically >100µm Yes Hydrocar-
chemical vapour multiple modified bons
deposition on tran-
sition metals

4.1.3. Tissue Engineering The superior electrochemical properties make it stand up

Dikin et al. demonstrated that graphene oxide sheets dis-
persed in water can assembled into well ordered structure
under a directional flows, yeilding ultra strong graphene ox-
ide. This graphene paper was used for culturing mouse fi-
broblasts cell line and the results confirmed graphene as a
good candidate for adhesion and proliferation of L929 cell.
Ryoo et al. studied the behaviour of NH-373 fibroblast cells
on graphene and suggested high biocompatibility of these
nanomaterials especially as surface coating materials for
implants without inducing a deleterous effect while enhanc-
ing some of the cellular function [33].
4.1.4. Cancer Targeted Therapy
Due to its unique conjugated structure, large surface area
and relatively low costs, graphene has open a new horizon in
the field of pharmacological applications in vitro and in vivo.
Graphene and its derivatives have been used for various
biomedical applications like anticancer therapy. Yang et al.
have studied in vivo tumour uptake and efficient protother-
mal therapy by intravenous administration of PEGylated
nanographene sheets (NGs) in several xenografts mouse
model. Shen and his coworkers used the multi functional
nanpcomposite based graphene oxide for in vitro heptacarci-
noma diagnosis and treatment [34].
4.1.5. Biosensors
The role of biomolecules in all life processes as well as in
disease development is imperative, hence disease diagnosis
and therapies require precise identification of biomolecules.
candidate for electrode material for better detection of bio-
molecules. Different biosensors made up of graphene deriva-
tives have their mechanism based on sensing which is inclu-
sive of electrochemical and optical signaling. Due to quick
response, high sensitivity, ease of operation and low cost
electrochemical approach to develop graphene-based biosen-
sors is appraised as best method for biomolecule detection
[35].
A promising application of graphene in sensing technol-
ogy is fluorescent detection due to excellent capability in
fluorescent resonance energy transfer (FRET). FRET refers
to the transfer of energy from a donor fluorophore to an ac-
ceptor fluorophore and its serves as one of the advanced
tools for measuring nanoscale distance and change. Gra-
phene was recently confirmed through theorotical and ex-
perimental studies to be a super quencher for organic dyes
and quantum dots [36]. Lu et al. reported the first graphene
based biosensor consisting of a dye labelled ssDNA probe
that could be bound and quenched by graphene oxide from
FRET effect between the dye and graphene oxide. Molecular
beacons(MBs) are elaborately designed DNA hairpins struc-
tures thar are dual labelled by a flurophore and a quencher at
two ends [37].
MBs provide more sequence specificity that linear probes
due to their inherant structural constraints thus they have
beeen widely used in genetic screening biosensors and bio-
chips, detection of single nucleotide polymorphism (SNP)
and mRNA monitoring in living cells. It has been reported
than graphene oxide quenched MB can detect DNA with
730 Current Drug Targets, 2017, Vol. 18, No. 6
higher senstivity and single base mismatch selectivity than
conventional MB. Kodali et al. used the nonpertubative
chemical modification of graphene for protein micropattern-
ing that are relevant to glucose sensor and cell sensor [38].
4.1.6. Graphene Oxide in Bio Imaging
Graphene oxide (GO) has been explored for biological
imaging due to the excellent biocompatibility, ready cellular
uptake, flexible chemical modifications and unique optical
properties. Tang et al. reported the DNA protection from
enzymatic digestion by the self-assembly of ssDNA on GO
sheets. After ssDNA adsorbed onto the GO surface no hy-
drolysis was observed by deoxyribonuclease (DNase) com-
pared to free ssDNA. ssDNA, which was firmly adsorbed on
a graphene surface, was effectively protected from enzy-
matic cleavage due to a steric hindrance effect that prevented
DNase I from binding to the DNA to initiate enzymatic di-
gestion. Due to this effect an opportunity has been opened
for the delivery of DNA/aptamer probes for in vivo imaging
of biomolecules in living cells [39].
Graphene oxide is an important material for magnetic
resonance imaging (MRI) in biomedical applications because
of its high light transmittance, photoluminescence, and high
charge mobility. Previously, superparamagnetic iron oxide
nanoparticles have been widely investigated for the applica-
tion of imaging. So, graphene oxide-iron oxide nanoparticles
functionalized with Polyethylene glycol (PEG) and loaded
with Doxorubicin (DOX) have been used for bioimaging
application [40].
4.1.7. Graphene in Photo Thermal Therapy
Apart from gene therapy, phototherapy is another thera-
peutic approach, which may be used to treat a variety of dis-
eases. Phototherapy, which includes photothermal therapy
(PTT) and photodynamic therapy (PDT), is able to control
disease by specific light irradiation. PTT employs an optical-
absorbing agent to generate heat under light irradiation, to
promote the selective destruction of abnormal cells biologi-
cal tissues are exposed to a raised temperature. Graphene has
received close attention from the PTT field due to its strong
optical adsorption in the near-infrared reflectance region.
Zhang et al. developed DOX-loaded PEGylated nano gra-
phene oxide (NGO-PEG (polyethylene glycol)-DOX), which
can deliver both the heat and drug to the tumorigenic region
to facilitate the combined chemotherapy and photothermal
treatment in one system. In vivo results demonstrated that the
designed approach was superior to chemotherapy or pho-
tothermal treatment alone [41].
4.1.8. Graphene as Antimicrobials
Few Attempts have been made to assay the toxicity of
graphene nanomaterials and their effect on microbes, which
may give contradictory results to prove their possible anti-
bacterial activity. Akhavan et al. described effect of gra-
phene “nanowalls” in membrane damaging of gram-positive
bacteria, though no membrane damage was observed using
gram negative bacteria. Non-reduced graphene oxide nanow-
alls were reported to be less toxic to microbes compared to
reduced graphene oxide nanowalls. In contrast, other studies
proposed graphene “paper” showing no effects on bacteria,
while photo-inactivation of Escherichia coli bacteria was
Ghuge et al.
reported on the surface of graphene/titanium oxide (TiO2)
composite films. The effects of different types of graphene
materials, namely graphite, graphite oxide, graphene oxide
and reduced graphene oxide (rGO) on a bacterial model (Es-
cherichia coli ) have also been assessed. The highest antibac-
terial activity was observed with GO followed by rGO, and
was thought to reflect the severity of membrane damage and
consequent oxidation stress caused [42].
4.2. Other Major Applications
4.2.1. Electronics
Outstanding physical properties of graphene makes it ex-
tremely appealing for application in electronics. In this ex-
traordinarly high carrier mobility µ has received most atten-
tion. Mobility in excess of 200,000 cm2/V.s have been re-
ported. In addition its thinnest mechanical strength and flexi-
bility of material, the fact that it has high current carrying
capacity and high thermal conductivity contributes to its
apppeal [43].
Graphene is a part of more complex structure and under
condition that are dictated by application itself. For example,
variety of scattering interaction are subject to electrical
transport. These include scattering through long range inter-
action with charged impurities, short range interaction with
neutral defects or adsorbates and by roughness and phonons.
The mechanism which will dominate the scattering depends
on the quality of the graphene itself and characteristic of
graphene exist [44, 45].
Because of high electrical conductivity, mechanical
flexibility and low cost graphene and its derivatives have got
wide spread application in LED, field effect transistor, tran-
parent conductive films, memory and photovoltaic devices
[46].
4.2.2. Transistor
Once carrier have been injected into the graphene their
transport can be controlled by a gate induced electric field. A
negatively bias applied to the gate raises electron energy
while a positively bias lowers it. In ambipolar graphene,
when EF is below neutrality point ENP (also referred to as the
dirac point) transport involve holes, while EF> ENPelectrons
are transported. As fermi energy is changed by the gates
Density of state (DOS) and corresponding the carrier density
(EF is proportional to square root of n) is changed. This is the
basis of ‘switching G’ in graphene field effect transistors
(GFETs) [47, 48]. This is a critical factor that determines
what role graphene plays in electronics.
The current on off ratio that can be achieved by gating of
a graphene transistor in the order of 10, the exact number
depending on the quality of graphene and effectiveness of
gating. Digital transistor utilized in logic applications, on the
other hand, it requires on /off ratio higher than about 10. It is
therefore clear that 2D graphene is not appropriate for digital
switch. While lack of band gap does not support its use as
digital switch, its outstanding carrier mobility, the high
transconductance of graphene devices and ultimate thinness
and stability of the material make it an excellent canditate for
fast analog electronics specifically radio frequency transis-
tors [49-52].
Graphene: A Comprehensive Review Current Drug Targets, 2017, Vol. 18, No. 6 731

Table 3. Correlation between properties, applications and products of graphene [14-56].

Application
Semiconductor
Transparent Conductive
Electronic Energy Storage Photonics Targeted Applications
Electrode
Devices
Parameters

High carrier High optical transmit- High surface area High electrical con- Efficient gene delivery.
mobility tance ductivity

Key Chemical tolerance Good adhesion and pro-

Graphene properties High electrical Light weight Graphene’s wide liferation of cells.
used conductivity spectral range
High electrical con-
Mechanical flexibility ductivity Good carrier material for
Mechanical flexi- various drugs.
bility
High electrical conductiv-
ity Used in Cancer therapies
and Tissue engineering
as a target material.

Products High frequency Touch panel Li-ion battery Photodetector Graphene nanomaterial
transistors based medicines.

E-Paper Super-capacitor Mode-locked solid

Logic transistors state laser Various devices made up
of graphene sheets as a
LED, OLED base.
Optical modulator

Smart window Carrier Target Material

in may therapies.

Solar cell

4.2.3. Graphene Photonics
Graphene has unique and tunable optical properties over
a wide length range. Moreover, the large wavelength of the
light makes this properties less dependent on local defects
and technological use of graphene easier. Theory based on
independent particle description of graphene predicts on op-
tical absorption for normal incidence photons in the energy
range where the dispersion of the Dirac cone is linear. More
recently, studies of graphene absorption reveals a richer be-
haviour [53, 54].
4.2.4. Energy Storage Devices
Having a high theorotical surface are of ~2630 m2g-1 and
ability to facilitate electrons or hole transfer along its 2-D
surface, graphene has been a promising material for elec-
trode. There have several reports on graphene based elec-
trodes for both rechargable lithium ion batteries (RLBs) and
electrochemical double layer capacitors (EDLCs). Graphite,
most commonly used anode material in rechargable lithium
ion Batteries (RLBs) has been replaced by graphene for its
superior electrical conductivity, high surface area and
chemical tolerance.
Energy storage devices such as lithium ion battery, Ultra
capacitor, Fuel cell and solar cell can make use of graphene
as a energy storage device [55, 56].
A quick rundown of graphene’s applications is given in
(Table 3).
CONCLUSION
The isolation of graphene in 2004 led to spectacular
growth in its utilization in different fields. Since, its innova-
tion it was an exciting material for field of physics and now
scientists have focused it for its use in wide range of funda-
mentals. Organic and material chemists are working hard on
new route to produce high quality single layers, while engi-
neers are designing novel devices to explore graphene’s ex-
traordinary properties. This review paper briefly discusses
the significant structural attributes of graphene. Starting from
it’s discovery the evolution in fabrication methods has been
732 Current Drug Targets, 2017, Vol. 18, No. 6
reviewed. Its unique characteristic properties those made it
an exciting material has been highlighted. A wide range of
utility in the area of targeted biomedical applications has
been mentioned as well as giving idea of its future scopes
and prospects in other areas also. Reviewing this complete
review about graphene it is very much clear that graphene is
indeed a best smart and nano material of present time and it
holds great promises to become one of the primary materials
of the times to come in the field of drug targetting as many
possible avenues of this exciting materials are yet to be un-
folded.
CONFLICT OF INTEREST
The authors confirm that this article content has no con-
flict of interest.
ACKNOWLEDGEMENTS
Declared none.
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