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Graphene Nano-ribbon Based high potential and Efficiency for DNA, Cancer
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Graphene nano-ribbon based high potential

and efficiency for DNA, cancer therapy and drug
delivery applications

Seyyed Mojtaba Mousavi, Sadaf Soroshnia, Seyyed Alireza Hashemi, Aziz

Babapoor, Younes Ghasemi, Amir Savardashtaki & Ali Mohammad Amani

To cite this article: Seyyed Mojtaba Mousavi, Sadaf Soroshnia, Seyyed Alireza Hashemi, Aziz
Babapoor, Younes Ghasemi, Amir Savardashtaki & Ali Mohammad Amani (2019): Graphene nano-
ribbon based high potential and efficiency for DNA, cancer therapy and drug delivery applications,
Drug Metabolism Reviews, DOI: 10.1080/03602532.2019.1582661

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DRUG METABOLISM REVIEWS
https://doi.org/10.1080/03602532.2019.1582661

REVIEW ARTICLE

Graphene nano-ribbon based high potential and efficiency for DNA, cancer
therapy and drug delivery applications
Seyyed Mojtaba Mousavia,b , Sadaf Soroshniac , Seyyed Alireza Hashemia,b , Aziz Babapoorc ,
Younes Ghasemia , Amir Savardashtakid and Ali Mohammad Amania
a
Department of Medical Nanotechnology School of Advanced Medical Sciences and Technologies, Shiraz University of Medical
Sciences, Shiraz, Iran; bPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; cDepartment of
Chemical Engineering, University of Mohaghegh Ardabili (UMA), Ardabil, Iran; dDepartment of Medical Biotechnology, Faculty of
Advanced Medical Sciences and Technology, Shiraz, Iran

ABSTRACT ARTICLE HISTORY

In this article, graphene oxide Nano ribbons (GONRs) and its high potential for using in medical Received 14 November 2018
fields have been reviewed. Recently, Graphene Nano ribbons (GNRs) has been a field of interest Accepted 11 February 2019
in biological methods and disease treatment such as drug delivery, DNA applications, and photo-
KEYWORDS
thermal cancer therapies. GNRs demonstrate more efficient properties rather than other gra-
Nano ribbon; anti-cancer;
phene-based Nanomaterials due to their larger surface area. These novel properties made them gene therapy; drug
into a remarkable substitute material for biological fields as they have different cytotoxic effects delivery; PEGylated
and almost nontoxic to human health and the environment. In this study, some of the significant
effects of GNRs such as Geno toxicity effects in human mesenchymal stem cells, DNA assembly,
drug delivery agents, and the use of PEGylated GNRs in photothermal cancer therapy has been
investigated.

1. Introduction obstacles still exist like their biocompatibility and deg-

Nanotechnology science has grown enormously in the
field of Nanomedicine (De Jong and Borm 2008;
€rster 2010; Kateb et al. 2011;
Kim et al. 2010; Oberdo
Abbaszadegan et al. 2017; Goudarzian et al. 2017).
Nowadays, carbon-based nanomaterials are broadly
used in several biomedical fields, such as photodynamic,
photothermal, radio therapies, imaging diagnosis, drug
delivery systems, and biosensor advancements (Akhavan
et al. 2012; Liu and Liang 2012; Hashemi et al. 2018;
Zakeri et al. 2018). So far, some particular carbon-based
nanomaterials hold exceptional physical and chemical
properties in comparison with other materials (Liu et al.
2007; Yang et al. 2010; Aslani et al. 2011; Amani et al.
2017; Nabavizadeh et al. 2017; Goudarzian et al. 2018;
Hashemi et al. 2018; Ravanshad et al. 2018); as they are
able to be loaded with a lot of drugs and compounds
as a result of their high surface area, and thus their sur-
face area of these carbon-based nanomaterials could be
adjusted with various bio functional groups. Although
these functional carbon Nano materials are extremely
effective for medicines as in cancer therapies (Akhavan
and Ghaderi 2010; 2012; Lu et al. 2014), some main
radation of those carbon Nano materials that must be
fixed for their future applications in medicine. CNTs have
been tried out for different in vivo cancer therapy, drug
delivery, and other medical applications for many years
and many groups have tested their use in animals world-
wide (Ma et al. 2011).
Therefore, one of the interesting shapes of carbon
materials, known as graphene is introduced which
contains novel properties such as antiviral (Akhavan
et al. 2012), bactericidal (Mohanty and Berry 2008;
Akhavan and Ghaderi 2009; Xu et al. 2011; Akhavan
et al. 2012; Ebrahiminezhad Bagheri et al. 2016;
Ebrahiminezhad Barzegar et al.2016; Gholami et al.
2016), disease diagnosis (Robinson et al. 2011), bio-
sensing (Zhang et al. 2011; Akhavan et al. 2012), can-
cer targeting (Markovic et al. 2011; Akhavan et al.
2012; Lu et al. 2014) and photothermal therapy (Liu
et al. 2008; Sun et al. 2008; Zhang et al. 2010), drug
delivery (Agarwal et al. 2010; Park et al. 2010; Li et al.
2011), and tissue engineering fields (Han et al. 2007;
Akhavan et al. 2013; Emadi et al. 2017). More on,
nanoribbon is one of the pioneer shapes of graphene

CONTACT Seyyed Mojtaba Mousavi mousavi.nano@gmail.com Department of Medical Nanotechnology School of Advanced Medical Sciences and
Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 S. M. MOUSAVI ET AL.
(GNR) which is actually the lengthened strips of sin-
gle-layer graphene with straight edges and a vast
length-to-width fraction (Zelphati and Szoka 1996;
Reuven et al. 2013).
As graphene presents charge delocalization proper-
ties, it has the potential chance of direct analysis in
biological molecules methods in the nano technology-
related fields (Boussif et al. 1995).
DNA based pairs have a crucial charge on them and
the combined phosphate backbone is a useful system
for the building nanoscale anisotropic biological fabri-
cations that will be able to examine by non-covalent
interactions with graphene (Okuda et al. 2004).
Recently, lots of efforts have been made to develop
non-viral gene path systems including liposomes (Lo
and Wang 2008), cationic polymers and dendrimers
(Behr 1993; Singh et al. 2005), polypeptides (Rosi et al.
2006), and other nanomaterials (Jia et al. 2007; Liu et al.
2007) for gene therapies. Compared to other patho-
logical carriers, these systems present more functions
for largescale production and better biocompatibility.
Besides, new delivery agents that are functionalized on
gold nano particles or carbon nanotubes are being
enormously explored for efficient delivery of drugs into
living (Liu et al. 2005; Li et al. 2008; Kosynkin et al. 2009;
Dong et al. 2011). As a result, graphene nanoribbon
(GNR) with straight edges (Barone et al. 2006) was
chosen for extensive experimental and theoretical stud-
ies (Colvin 2003; Hussain et al. 2009; Zhang et al. 2010).
2. Graphene nano ribbon
Graphene, which consists of two-dimensional single-
layered graphite mesh network, has got incredible
attention in recent years for a wide range of clinical
applications.
Comparing to one dimentional graphene sheets
such as carbon nano tubes (CNTs), two-dimensional
graphene sheets (GNRs) are estimated to have notable
different cytotoxic effects (Novoselov et al. 2005; Kang
et al. 2008; Akhavan et al. 2009; Jiao et al. 2009; Chang
et al. 2011). Because these nanostructures symbolize
chemical composition with crystalline structure so they
are different in shape and thus their interactions with
biological systems would not be administrated with
same mechanism. Meanwhile, the main subject of
investigation for any particular biological application is
the potential cytotoxic and genotoxic influences of
nanomaterials for human health and environments. For
this reason, the cytotoxic effects of neural phaeochro-
mocytoma-derived.
PC12 cells with graphene was studied (Kang et al.
2008) and the results revealed time-dependent cyto-
toxic effects of reactive oxygen species (ROS) involved
with graphene. Also, it was reported that (Morozov
et al. 2005) graphene oxide was unable to enter A549
cell and has no visible cytotoxic effects; but, cells
showed concentration-dependent oxidative stress and
led to a minor cell viability loss at high concentrations
(_100 lg/mL). It was also shown that one of the main
cytotoxic mechanism of graphene oxide is as a result of
graphene’s highly sharp edges contact interaction with
nano walls direct contact interaction of extremely sharp
edges of graphene Nanowalls with cell wall membrane
of bacteria (Zelphati and Szoka 1996; Akhavan and
Ghaderi 2009).
The structure of GO nanoribbons (GONRs) is
grounded on unzipping of one-dimensional (CNTs) and
two-dimensional graphene carbon nanomaterials
(Novoselov et al. 2004; Barone et al. 2006).
Graphene ribbons present a well-defined two-
dimensional structure useful for electronic environments
and controlling non covalent interactions (Zhang et al.
2006). Planar zigzag edged GNRs has a great potential
for bio diagnostics, DNA Nano electronics, bio-sensor
devices, spintronic, and Nano electronics (Zhang et al.
2005; Wang et al. 2008; Choi et al. 2010; Samarakoon
and Wang 2010). Furthermore, GNRs based on metal
materials and lithographic methods have been manufac-
tured (Colvin 2003; Min et al. 2007; Manohar et al. 2008),
as well as oxidative longitudinal unzipping method of
multiwall carbon nanotubes (MWCNTs) (Barone et al.
2006; Samarakoon and Wang 2010; Ahmed et al. 2012).
With treating GNRs with Oxidative chemicals they result
in the oxygen species alternation of the basal plane
and edge with a carboxylic acid, epoxide, hydroxyl, and
carbonyl groups (Okuda et al. 2004).
3. GNRs geno toxicity effects in human
mesenchymal stem cells
Single layered reduced graphene oxide nanoribbons
(rGONRs) were modified by oxidative unzipping of
multi-wall carbon nanotubes and subsequent deoxy-
genation of bovine serum albumin and hydrazine.
Then, isolated human mesenchymal stem cells (hMSCs)
from umbilical cord blood was used for the time
dependent, concentration cytotoxicity, and Geno tox-
icity effect of rGONR.
The genotoxicity of rGONRs in lower concentrations
was also studied as the DNA damage of cells in one
of the effective parts which are involved in the cell
destruction.

Figure 1. DNA fragmentation of hMSCs. Controlled results are marked with
(Zelphati and Szoka 1996).
Figure 2. Surviving hMSCs after exposure the rGONRs. Controlled results are marked with
and 0.01 (Zelphati and Szoka 1996).
Figure 1 presents the concentration and time-based
DNA fragmentation of hMSCs exposed to the rGONRs
in terms of the percentage of DNA in the tail which
gets higher with the increase of rGONRs concentration.
It was also revealed that the concentration-dependent
cytotoxicity of the rGONRs was started at 10 lg/mL after
1 h of time exposure (see Figure 2), but the DNA was
fragmented at a lower concentration of 1.0 lg/mL.
It is revealed that the high mobility and extremely
sharp edges of the nanoribbons penetrates the rGONRs
into cells, and the DNA fragmentation has considerably
raised with concentration and time increase. Also, it was
indicated that the rGOSs only exhibited minor DNA dam-
age after 96 h time exposure to 100 lg/mL of the sheets.
Figure 3 also shows the rGONR penetrated into the
nucleus of cells with blue color stained by DAPI, and
DRUG METABOLISM REVIEWS 3
*
and **
symbols for p values <0.05 and 0.01
*
and **
symbols for p values <0.05
the green color represents the existence of cy3-labeled
rGONR-PEG. Thus, these results proved the shape
dependent effect of graphene sheets and nanoribbons
interaction with stem cells (Zelphati and Szoka 1996).
4. Supramolecular assembly of DNA on
graphene nanoribbons
Recent studies have determined that GNRs surface
coated with SiO2 will present a precise self-assembling
electronic environment as a result of straight edges and
free of strain effects ability compared to other forms of
graphene (Okuda et al. 2004). It was also revealed that
GNRs impose anisotropic assembly of single-stranded
DNA (ssDNA) into ribbon-shaped structures on a unique
direction dependent morphology which was never
4 S. M. MOUSAVI ET AL.
Figure 3. (a) Nucleus of the cells stained by DAPI (blue). (b) Cell nucleus exposed to 100 lg/mLrGONR-PEG labeled by cy3 (green)
Fluorescent imaging (Zelphati and Szoka 1996).
seen on any other forms of graphene oxide. GNRs were
also approved to generate a covalently closed circular
double-stranded DNA called pComb-5 plasmid into hex-
agonal ordered films. These results also illustrated that
GNRs are potential agents for nucleation site of multi-
micron formation of DNA films (Barone et al. 2006;
Ahmed et al. 2012). The estimated height of unzipped
GNRs was about 0.50–0.75 nm and the width was about
400–500 nm. Figure 4 shows the organization of supra-
molecular DNA segments at 30 mM strand concentra-
tions on the GNR, respectively. Oligo A, G, T, and C are
expected to exist as disordered single strands in the
solution (Nelson et al. 2010).
Results also illustrated that the Branches at the end
of assembled patterns which were assigned to the lack
of underlying GNR “support,” revealed the high cap-
ability of GNRs as an adhesive biological platform for
supercoiled pComb-5 plasmid51, high molecular
weight DNA, and herring sperm DNA onto GNR with
SiO2 coated surface (Liu et al. 2007; Yang et al. 2008;
Kostarelos et al. 2009; Schneider et al. 2010).
Dispersion-corrected DFT calculations also proved
that graphene is more tightly bounded and transferred
on nucleotide base-oriented comparing to the phos-
phate oriented end. In summary, it could be concluded
that ssDNA has critical attractions with GNRs. DFT and
Raman studies obviously showed the donation of elec-
trons in ssDNA leads to critical changes in the electronic
properties of GNRs (Okuda et al. 2004).
5. Nano ribbons as drug delivery agents
Carbon nano materials have been reported to activate
various mechanisms such as toxicity and drug delivery,
but yet they may cause some side effects in long terms
(Chan et al. 2008). A pioneer research on drug delivery
of nano materials showed noticeable tumor targeting
effects (approximately 13% injected dose/g) of Carbon
nano tubes for cancer therapies (Akhavan and Ghaderi
2010) and they also showed an ultra-high doxorubicin
(DOX)-loading capacity (almost 400% by weight) for
drug delivery (Cavalieri et al. 2008). Furthermore,
PEGylated biocompatible Nano graphene oxide was
prepared as a drug carrier (Agarwal et al. 2010), which
resulted in high water solubility and stability in the
plasma. On another study, the common anticancer drug
(SN38) was loaded onto a PEGylated Nano graphene
oxide using p-p interactions (Sun et al. 2008). Since gra-
phene oxides (GOs) has a significant loading capacity,
DOX was loaded on nearly 235% by weight, which was
very high compared to other pharmaceuticals such as
polymeric micelles (Moon et al. 2009), hydrogel micro
particles (Zhou et al. 2009), and liposomes (Ghosh et al.
2009), which cannot be loaded with more than approxi-
mately 100% DOX by weight. These and many other
findings revealed the potential of functionalized gra-
phene-based applications for controlled drug delivery in
biomedical applications (Ma et al. 2011).
5.1. Polyethylenimine-grafted GNRs for cellular
delivery for microRNA recognition
Polyethylenimine-grafted graphene nanoribbon (PEI-g-
GNR) is introduced as an Effective gene vector and
drug carrier. For this case, GNRs were formed by using
longitudinally unzipping multiwall carbon nanotubes
(MWCNTs) method. Then, electrostatically assembly
and sonication was used to treat the strong acids and
surface carboxylic acid groups for grafted PEI.
 DRUG METABOLISM REVIEWS 5

Figure 4. AFM 3D images of supramolecular ordered 20 bases sDNA oligomers A (a), G (b), AT (c), T (d), C (e), and GC (f) on the
GNR surface. Bottom insets: cross-sections of ssDNA–GNR nanocomposites of A, G, AT, T, and CGNR composites. This shows the
axially aligned bundled rope like structures profile, with overlapping lamella architecture of GC–GNR composites (Okuda et al. 2004).

The nano carrier ability was observed by PEI-g-GNR
protecting locked nucleic acid modified Molecular bea-
con (LNA-m-MB) from nuclease digestion or single-
strand binding protein interaction, the high charge
density of PEI, and the large surface area of GNRs.
The TEM image (Figure 5) revealed the size-depend-
ent gene vector potential of GNR with the average
width of the GNR to be 70e130 nm, which was just
about 3.14 times of the original MWCNTs.
Confocal microscopic imaging showed the capability
of PEI-g-GNR as gene vector for LNAm- MB transfer
with remarkable affinity and specificity to miRNA target
into HeLa cells for miRNA detection. The results demon-
strated that all of the PEI-g-MWCNTs, PEI-g-GNR, and
PEI delivered the LNA-m-MB into the cells, and the tar-
geted miRNA was totally recognized by producing
green fluorescence as a result of separating the dye
from the quencher labeled to MB (Figure 6). The cyto-
toxicity of PEI-g-GNR Nano carriers were very low and
protected the LNA-m-MB from nuclease digestion or
SSB interaction. These results proved PEI-g-GNR as a
promising non-viral vector for gene therapy and clinical
application (Zhang et al. 2010).
6. The potential of GNRs on cancer therapies
Photo thermal therapy with nano materials and strong
absorption of near-infrared (NIR) light has gained more
attention during the past few years compared to any
other cancer treatment of advanced-stage cancers such
as surgery, chemotherapy, radiotherapy, and sometimes
a combination of them (Coates et al. 1983; Sun et al.
2008; Agarwal et al. 2010; Li et al. 2011; Markovic et al.
2011; Akhavan et al. 2012; Ma et al. 2012; Lu et al. 2014;
Gholami et al. 2016; Emadi et al. 2017). Other treatments
are known to offer significant disadvantages including
severe adverse reactions (Szakacs et al. 2006; Splinter
2007) and low competence against resistant cancer cells
6 S. M. MOUSAVI ET AL.
Figure 5. (a) TEM image, (b) AFM image and (c) Raman spectra of as-prepared GNR, and (d) expanded region of D and G bands
from panel (c) (Zhang et al. 2010).
(Hu et al. 2010; Shao et al. 2010). But, photo thermal
treatment depends on photoexcitation of attaching
photosensitizing agents to cancer cells for overheating
and consequently wrecking the cells (Heo et al. 2011).
One of the first in vivo fluorescent imaging and
photo thermal treatment of cells (Lu et al. 2014)
using Nano graphene sheets functionalized by poly-
ethylene glycol (PEG) (Ma et al. 2012) resulted in the
influence of surface chemistry and size related effects
of Nano graphene oxide sheets on performing photo
thermal cancer treatment. Later, in vitro investigation
of phototermal therapy on low concentration (6.6 mg
mL_1) of reduced Nano graphene oxide–PEG sheets
was also reported (Markovic et al. 2011). The syner-
gistic effect of combined chemo-photo thermal treat-
ment with graphene oxide–PEG was reported by
Zhang et al. (Sun et al. 2008) and Markovic et al. (Liu
et al. 2008) too. They demonstrated a better in vitro
photo thermal performance of graphene nanopar-
ticles coated with polyvinylpyrrolidone compared
DNA or sodium dodecyl benzenesulfonate-solubilized
single-wall carbon nanotubes (SWCNTs). Later, using
a biocompatible glucose-reduced graphene oxide
(with-out any PEGylating) in comparison with per-
formances of SWCNTs and multi-wall carbon nano-
tubes (MWCNTs) were also reported for photothermal
therapy (Roth and Cristiano 1997; Zhang et al. 2010;
Sun et al. 2011).
In most of these investigations, PEGylated Nano gra-
phene sheets were used to achieve a reliable photo
thermal effect, since they exhibited a variety of interest-
ing in vivo features, including highly efficient tumor
passive targeting, strong NIR absorbance, and fairly
low retention in mononuclear phagocyte systems, and
apparently no visible side effects (Akhavan et al. 2012;
Lu et al. 2014).
6.1. PEGylated GNRs for selective cancer cell
imaging and photo thermal therapy
Recently, graphene oxide nanoribbons were reduced
and functionalized with amphiphilic polyethylene

Figure 6. Confocal images of transfected HeLa cells with LNA-m-MB/PEI-g-GNR at 37 (a–c) and 4 _C (d–f) for 1 h: fluorescence
field (a,d), bright field (b,e), and overlapped images (c,f) (Zhang et al. 2010).
glycol (rGONR– PEG) and cyanine dye 3 (cy3) and argin-
ine-glycine-aspartic acid (RGD)-based peptide were
attached to them for anb3 integrin receptors targeting
on human glioblastoma cell line U87MG and with
selective fluorescence imaging, respectively.
After PEGylating of the rGONR, strong C–H
(_2850 cm_1), CO–NH (_1640 cm_1), and C–O
(800–1500 cm_1) stretch peaks appeared which evidently
showed the conjugation of PEG to the rGONR–PEG (Sun
et al. 2008; Ma et al. 2012). rGONR–PEG was highly
absorbed and offered effective photothermal heat.
Similarly, the transparency of the GONR suspension a
minor heating up to 32 C after 10 min of irradiation.
But on the other hand, rGONR–PEG on low concentra-
tion (1.0 mg mL_1) showed 50  C of photothermal heat-
ing under NIR within the 6.5 min of irradiation. Figure
DRUG METABOLISM REVIEWS 7
7(a) shows the effective cancer cell targeting and the
green color represents the existence of cy3-labeled
rGONR–PEG on the cells while no special targeting was
observed for the control. Thus, these results will confirm
the positive selective targeting of the anb3 integrin
receptors cancer cell lines by the RGD-conjugated
rGONR–PEG (Akhavan et al. 2012).
7. GNRs as gene delivery agents
Gene therapy has been an interesting field for treating
cancer (Alton et al. 1993; Levasseur et al. 2003;
Margaritis et al. 2004), hemophilia (Dodart et al. 2005),
cystic fibrosis (Soutschek et al. 2004), sickle cell anemia
(Kawabata et al. 1995), and Alzheimer (Chowdhury et al.
2013). Bulk genetic materials will collapse very soon and
8 S. M. MOUSAVI ET AL.
Figure 7. (A) Fluorescent imaging and (B) emission spectra of the glioblastoma incubated cells with (a) rGONR–PEG–cy3–RGD
and (b) rGONR–PEG–cy3–RAD. (B) the fluorescence intensity of the incubated cells with the rGONR–PEG–cy3–RGD is about 8.5
times the Intensity of the cells the rGONR–PEG–cy3–RAD (Akhavan et al. 2012).
they indicate a very short serum half-life such as about
1 min for RNA and 10 min for DNA because of their low
bioavailability and entry into target cells (Chowdhury
et al. 2014, 2015). Hence, the improvement of gene
delivery agents for more efficient transfer and overcom-
ing the main cell barriers is considered. These barriers
include the stable loaded or conjugated negatively
charged DNA or RNA into molecules, then, cells will
take up the delivery agent both by endocytosis or
micropinocytosis, and at the end, the delivery agent has
to enter the nucleus in order to deliver the DNA. Recent
studies showed a great cellular response and drug deliv-
ery ability from O-GNR-based nanoparticles that were
different from other carbon materials (Reuven et al.
2012; Chowdhury et al. 2015; Youn et al. 2015).
Herein, bulk O-GNRs were served as a multipurpose
platform for drug loadings on large amounts of genetic
material. As a matter of fact, reduced graphene oxide
has a bigger surface area and gradually is more efficient
for drug loading systems (Zhou et al. 2012; Zhang et al.
2013). Also, it has been revealed that oxygen-contain-
ing graphene oxide is more suitable for drug delivery
injections. However, non-oxidized graphene nanorib-
bons maybe more appropriate for other clinical applica-
tions such as in biosensors in which higher surface area
is an important factor for assembling polymers and
DNA on the surface of nanoribbons (Okuda et al. 2004;
Yin et al. 2013).
Directly loaded O-GNRs with genetic materials have
been reported for the first time during the past decade.
On the other hand, a wide range of GO-based materials
has been resulted into being highly unstable in physio-
logical buffer solutions (Mullick Chowdhury et al. 2016).
Thus, functionalization of GO and GNRs will lead to a
higher surface area and more drug loading capacities.
7.1. GNR platform for nuclear gene delivery
The oxidized graphene nanoribbons (O-GNRs) is a non-
viral vector for gene therapy and in vitro studies. It has
been reported that bulk O-GNR is able to load a large
amount of genetic materials in different sizes without
any functionalized positively charged groups or other
non-viral vectors. For this case, the cytotoxicity analysis
was taken using MRC5 lung fibroblast cells.
Thus, Fugene 6 and PEI were used as transfection
agents and they were incubated at 0.5 mg/mL for PEI
and 2.4 mL per well total for Fugene 6 with same period
of time for control. Compared to untreated control, cells
treated with 100 mg/mL of OGNRs at did not show any
noticeable amount of cell death. But, Fugene 6 incu-
bated cells showed 25% released LDH in comparison
to untreated control, then, PEI treatments showed
60% of LDH release that suggests O-GNRs as poten-
tially safe material for the 100 mg/mL concentration.
These results are also same the previous O-GNRs

Figure 8. (a c,f g) Confocal microscopy pictures of HUVEC and HeLa cells treated with various concentrations of EGFP plasmid
loaded O-GNRs. nuclear staining with Hoechst stain and EGFP expression is visible in cells treated with (a) 20, (b) 40, and (c)
60 lg/mL GNR (d,i).
toxicity experiments in HeLa cells where functionalized
O-GNRs remain nontoxic long as they were not treated
by high probe sonication.
Figure 6 shows the efficient gene delivery results
from HUVEC and HeLa and cells that was treated with
siRNA (against GAPDH) EGFP plasmid loaded OGNRs
for 12 h.
Figure 8(a–c,f–h) illustrates the stained nucleus and
EGFP fluorescence of the treated HUVEC and HeLa cells,
respectively.
Figure 8(e) also shows the loaded O-GNRs increased
concentration GAPDH enzyme activity of HeLa cells
exposed to siRNA against GAPDH (0 60) mg/mL) for 12 h.
Thus, the results confirmed a dose-dependent
decrease of GADPH activity. The gene delivery results
clearly Implied that by increasing the exposure of O-
GNRs, more EGFP plasmid and siRNA will reach the
nucleus of the cells. Furthermore, gene transfection effi-
ciency was very high (96–98%) such as the percentage
of cells with visible GFP fluorescence was same for both
cells at all tested concentrations (measured by observing
fluorescence in 300 cells exposed to each concentration).
8. Conclusion
In the present study, graphene Nano ribbons (GNRs)
were chosen to be investigated in the field of medical
DRUG METABOLISM REVIEWS 9
science, as a result of their novel properties over other
graphene-based materials, such as carbon Nano tubes.
Results indicates the high potential of GNRs to be used
as an effective agent on drug delivery, DNA assembly,
anti-cancer, and photo thermal therapies. The effective
concentration-dependent Geno toxicity effects in
human mesenchymal stem cells was reported using an
oxidative unzipping the multi-wall carbon nanotubes
and a subsequent deoxygenation by hydrazine and
bovine serum albumin, single-layer reduced graphene
oxide nanoribbons. Furthermore, GNRs was used for a
drug carrier as they present a huge amount of DOX-
loading capacity (about 235% by weight) rather than
other materials. Also, polyethylenimine-grafted GNRs
was used for cellular delivery in order to recognize
microRNA with low toxicity. Thus, the results revealed
that PEI-g-GNR would be a positive non-viral agent in
gene therapy and clinical application. At the field of
cancer therapy, photo thermal treatments using Nano
materials, especially GNRs has been widely developed
during the recent years, as they have almost zero side
effects and being nontoxic to human health and envir-
onment rather than other chemo therapy materials. In
order to reach this state, graphene oxide nanoribbons
were reduced and functionalized by amphiphilic poly-
ethylene glycol (rGONR–PEG) and attached to arginine-
glycine-aspartic acid (RGD)-based peptide and cyanine
10 S. M. MOUSAVI ET AL.
dye 3 (cy3)for targeting anb3 integrin receptors on glio-
blastoma cell line U87MG, respectively. Also, gene deliv-
ery is considered as another promising field of using
GNRs. Nano ribbons were used in gene delivery as they
are much more stable than other agents and presenting
low side effects. Therefore, MRC5 cells were chosen for
this investigation, and the results demonstrated that O-
GNRs are able to load the different sizes of stranded
genetic materials, without adding any other non-viral
vectors or functionalized positively charged groups.
Thus, it’s believed that GNRs have a bright future in the
field of modern medical treatments.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Seyyed Mojtaba Mousavi http://orcid.org/0000-0002-
3500-877X
Sadaf Soroshnia http://orcid.org/0000-0003-1926-1406
Seyyed Alireza Hashemi http://orcid.org/0000-0002-
4713-6883
Aziz Babapoor http://orcid.org/0000-0003-4907-2462
Younes Ghasemi http://orcid.org/0000-0003-4172-0672
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