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Khan et al

Tropical Journal of Pharmaceutical Research July 2014; 13 (7): 1169-1177


ISSN: 1596-5996 (print); 1596-9827 (electronic)
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
All rights reserved.

Available online at http://www.tjpr.org


http://dx.doi.org/10.4314/tjpr.v13i7.23
Review Article

Gold Nanoparticles: Synthesis and Applications in Drug


Delivery
AK Khan1, R Rashid 1
, G Murtaza2* and A Zahra1
1 2
Department of Chemistry, Department of Pharmacy, COMSATS Institute of Information Technology, 22060 Abbottabad,
Pakistan

*For correspondence: Email: gmdogar356@gmail.com; Tel: +92-314-2082826; Fax: +92-992-383441

Received: 3 April 2014 Revised accepted: 2 June 2014

Abstract
This review is focused essentially on the synthesis and applications of gold nanoparticles in the field of
medicine and targeted drug delivery. Nanotechnology has become one of the most interesting and
advanced areas of research in this field. Among nanoparticles, gold nanoparticles demonstrate special
advantages in this field due to their unique properties, small size and high surface area-to-volume ratio.
These particles have been widely used in various biomedical applications and drug delivery systems
due to their inert nature, stability, high dispersity, non-cytotoxicity and biocompatibility.

Keywords: Biosynthesis, Gold nanoparticles, Biomedical applications, Targeted drug delivery,


Nanotechnology.

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INTRODUCTION optical and electrical properties which make them


different and more applicable than large size
The term nano is derived from the Greek word materials. Nanoparticles are proved to be
nanos which means small and it is used as the promising multi-functional platform because they
prefix for one billionth part (10-9). According to can be used for many imaging and therapeutic
American Society for Testing and Materials functions. These types of platforms can be
(ASTM international 2006), nanoparticles are synthesized by different organic , inorganic or
those particles which have two or more than two hybrid of organic and inorganic materials but
dimensions and are in the size range of 1 - 100 among all these inorganic platforms are of most
nm [1]. These particles have special and important for diagnosis and simultaneous therapy
enhanced physical and chemical properties as due to their easy modification, stability and high
compared to their bulk materials due to their drug loading capacity [3].
large reactive and exposed surface area and
quantum size effect as a result of specific Recently much attention has been paid towards
electronic structures. These particles have been controlling the shape and size of metal
widely used in many fields such as electronics, nanostructures because all the magnetic,
photochemical, biomedicine and chemistry [2]. catalytic, electrical and optical properties of metal
nanostructures are influenced by their shape and
Inorganic nanoparticles and combination of size. Nanoparticles have wide applications in the
inorganic nanoparticles with organic materials to field of biomedicine such as to deliver
form hybrids possess unique physical, chemical, pharmaceutics, for diagnostic approaches as well

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as for the therapeutic purposes because reduced side effects as compared to the
nanoparticles have very small sized particles, conventional drugs, which have been used for
they can be used for targeted drug delivery and cancer treatment. Main properties of
the metallic nanoparticles respond resonantly to nanoparticles to be an effective drug delivery
the magnetic field which varies with time so they agent includes monodispersity, lack of
transfer enough toxic thermal energy to the cytotoxicity and simple mechanism of interaction
tumor cells as hyperthermic agents [4]. Metal with desired ligands. One the basis of these
nanoparticles specifically gold nanoparticles characteristics many nanoparticles have been
have abundant use in the field of biotechnology synthesized and used in cancer treatment, drug
and biomedicine because they have large delivery systems and imaging such as
surface bio conjugation with molecular probes dendrimers, quantum dots, polymer gels, gold
and they also have many optical properties which nanoparticles, ZnO, or Fe2O3 [9]. Various
are mainly concerned with localized plasmon chemical and physical methods have been
resonance (PR) [5]. adapted for the synthesis of nanoparticles which
are quite expensive and the chemicals used are
Nanoparticles cover a broad area of interest harmful to the environment. To overcome these
including electronics, medicine, food industry, problems green synthesis is emerging field of
environmental applications and cosmetics. research of current era. Inorganic nanoparticles
Furthermore due to the metallic properties these have particular application in molecular imaging
metal nanoparticles exhibit photoelectric effect as contrast agent such as magnetic resonance
which neutralizes the photo bleaching concerns imaging (MRI), positron emission tomography
related with the conventional fluorescent dyes. (PET), computed tomography (CT), ultrasound
Surface modification of the nanomaterials have and optical imaging [10]. This review focuses
strong effect on the interaction of these gold nanoparticles as important area of research
nanomaterials with cells, in addition to this it also regarding biomedical applications especially in
helps to convert toxic nanomaterials to the less cancer therapy.
toxic or less toxic to more toxic nanomaterials [6].
Nanoparticles have been used to enhance the GOLD NANOPARTICLES
selectivity and efficiency of the drug delivery
system because they act as mediators of drug Properties of gold nanoparticles are different
release. Nanoparticles have extremely small size from its bulk form because bulk gold is yellow
and high surface area hence their surfaces has solid and it is inert in nature while gold
been available for further modification with nanoparticles are wine red solution and are
hydrophobic, hydrophilic, cationic, anionic or any reported to be anti-oxidant. Inter particle
neutral moieties to the surrounding environment interactions and assembly of gold nanoparticles
so they have many application in biological networks play key role in the determination of
sciences. properties of these nanoparticles [11]. Gold
nanoparticles exhibit various sizes ranging from
Drug delivery systems based on nanoparticles 1 nm to 8 m and they also exhibit different
have proved to be a great route for targeting shapes such as spherical, sub-octahedral,
malignant brain tumors where the conventional octahedral, decahedral, icosahedral multiple
therapy is not as much effective. Enhanced twined, multiple twined, irregular shape,
permeability and retention (EPR) is the unique tetrahedral, nanotriangles, nanoprisms,
property of nanoparticles to accumulate and hexagonal platelets and nanorods (Figure 1).
interact with the tumor cells [7]. Platelets plays a
vital role in the development of cardiovascular
diseases so the antiplatelet agents are
considered as the necessary components for the
curing such diseases. Therefore, the interaction
of nanoparticles and the vascular pathway
becomes an essential part of the management
and prevention of cardiovascular disease.
Among all metallic nanoparticles the gold
nanoparticles proved to be the safest and much
less toxic agents for drug delivery and for
hyperthermic agents for the cancer treatment [8].
Nanotechnology induced advance approaches in
the field of biomedical sciences specially related
to the cancer therapy and for diagnostic
Figure 1: Various shapes of gold nanoparticles
applications regarding efficient drug delivery and

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Among all these shapes triangular shaped Gold nanoparticles are widely used in biomedical
nanoparticles show attractive optical properties science including tissue or tumor imaging, drug
as compared to the spherical shaped delivery, photo thermal therapy and immuno-
nanoparticles. Using of single active substance chromatographic identification of pathogens in
from plant extract in the synthesis of gold clinical specimens due to the surface plasmon
nanoparticles is an important bio synthesis resonance (SPR) [17]. Nanoparticles have
technique to purify gold nanoparticles and to unique physiochemical properties including
investigate about their medical uses. Gold surface area, amphilicity, shape,
nanoparticles have been widely used in the field biocompatibilities and surface carrier capabilities
of radiation medicine as radiation enhancer [12] which make them suitable for gene delivery, as
and also provide therapeutic enhancement in the function of conjugated gold nanoparticles
radiation therapy due to the efficient and targeted described by various factors such as protein
drug delivery to the tumor site. Gold structure, particle morphology and conjugated
nanoparticles have various applications as strategy [18]. Gold nanorods have various
platform nanomaterials for biomolecular applications in the field of in vivo imaging due to
ultrasensitive detection, killing cancer cells by the plasmon resonance absorption and
hyperthermal treatment, labeling for cells and scattering of light in the near infrared region [19].
proteins and delivering therapeutic agents within Colloidal gold nanoparticles have also gain much
cells. attention due to their easy preparation through
chemical methods and they can easily be
Fluorescent nanoparticles or nanoprobes based imported to the tissues and cells because of their
on gold nanoparticles have good biocompatibility very small size which is equal to the biological
for molecular imaging of many enzymes and molecules like DNA and proteins [20].
metabolites which is necessary for cellular
functions in cancer. Gold nanorods have gained Gold nanoparticles can bind with a wide range of
much attention in recently few past years due to organic molecules as they have low toxicity and
their specific optical and chemical property and tunable physical and chemical properties so they
hence used for biological applications [13]. Gold have been used as therapeutic agents or vaccine
nanorods have unique anisotropic geometry carriers in to the specific cells so that they can
which enables them to get tunable absorption in increase the efficiency of drugs and can destroy
both visible and near infrared (NIR) regions and pathogens. By using gene gun gold
make them suitable for potential applications in nanoparticles have been extensively used for
the fields of biosensing, gene delivery and photo epidermal delivery of DNA vaccines and this
thermal therapy. Gold nanoparticles have various method is one of the best methods to deliver
advantages over conventional iodine-based DNA vaccine. Coated walls of gold nanocages
agents as gold has higher absorption coefficient with temperature-sensitive polymer were used as
than iodine due to its higher atomic number and drug carrier which releases their effectors with
electron density so it enhance CT contrast more interaction of near-infrared irradiations [21]. Gold
than iodine so they have been used in X-ray CT nanoparticles having small size and diameter
imaging as molecular probes [14]. about 1 nm are able to cross the cell membrane
and nucleus to interact with DNA on the contrary
The second major advantage of gold gold nanoparticles of size 18 nm exhibit excellent
nanoparticles is that they are non-cytotoxic and penetration in to cells but cytotoxicity was not
third most important benefit is regarding their observed [22].
surfaces, as they have large surface area due to
which their surfaces are readily available for Gold nanoparticles have strong affinity for
modification with targeting molecules or specific alkynes as compared to other transition metal
biomarkers and applicable in biomedical catalysts but the homogeneous systems are not
purposes [15]. The role of gold nanoparticles in favorable economically and environmentally
biological sciences is very important because of because of rapid reduction of active gold
the compatibility, conjugation of these particles to complexes in to inert metallic gold during the C-H
the biomolecules and their tunable optical alkyne activation. Due to the unique optical and
properties which are due to the shape, size and electronic properties of gold nanoparticles they
surface area of the gold nanoparticles. Due to have been widely used in the color indicating
the small size and large surface, shape and probes in the development of analytical
crystallinity, nanoparticles are proved to be techniques which are used for the sensing of
excellent therapeutic agents because they can various analytes [23]. Gold colloids have been
easily travel into the target cells and can bear used in the surface modification of ideal
high drug load [16]. electrodes due to their remarkable stability and
unique properties including high biocompatibility

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which is necessary to retain the native structure dendrimers by sodium borohydride [59]. Mathias
and enzymatic activity of attached proteins or Ulbricht and co-workers reported the direct and
enzymes. Combination of gold nanoparticles into one-step synthesis of water soluble gold
smart polymer like poly (N-isopropylacrylamine) nanoparticles of size < 10 nm with two different
is an effective process to enhance the various thiols including 1-mercaptoundec-11-yl-hexa
properties of polymer such as showing swell of (ethylene glycol) (EG6) and dodecanethiol (C12)
collapse reversibility in response to the [29].
temperature stimuli [24].
A non-seed mediated temperature synthesis
SYNTHESIS STRATEGIES method of gold nanoparticles has been
developed. In this method gold nanoparticles
Various methods have been developed for the having mean diameter of 75 + 10 nm were
synthesis of gold nanoparticles and these prepared by the reduction of gold ions in
methods follows the same rules as the ethylene glycol with NaOH as reducing agent
preparation methods of other particles [25]. [30]. Flow micro-reactor system is applied for the
General methods for the synthesis of gold synthesis of gold nanoparticles by the reduction
nanoparticles include chemical, physical, and of gold (III) chloride complex ion through glucose
biological methods which are explained below. as reducing agent and poly vinyl pyrrolidone
(PVP) as a stabilizing agent [4]. The highly stable
Chemical methods gold nanoparticles of size 7.8 + 1.7 nm have
been synthesized through reduction of HAuCl4 by
Gimenez et al proposed a method to synthesize sodium borohydride as reducing agent. In this
gold nanoparticles supported on an insoluble method bovine serum albumin was used as
thiolated chitosan derivative by reduction of the capping agent and protein capped gold
HAuCl4 through thiolated chitosan (QTDT) as nanoparticles were reported [6]. In 2013, Kawai
reducing and coupling agent for gold and co-workers synthesized organogels which
nanoparticles so the synthesized QT/Aunano is were used as template for the preparation of gold
used as a good catalyst for the reduction of nanoparticles by reduction method [64].
methylene blue [26]. Citrate thermo reduction
method was used for the synthesis of gold Surfactant assisted method has been used for
nanoparticles having efficient SERS (surface the synthesis of partially functionalized gold
enhanced Raman spectroscopy) in short reaction nanoparticles by using a bifuntional ligand
time by using a low cost reagent inositol hexadecyl trimethyl ammonium bromide (CTAB)
hexaphosphate (IP6) as reduction agent for as linker between solid substrate and gold
HAuCl4 [27]. Another method used for the nanoparticles [9]. Hot injection technique is
synthesis of thermo-sensitive gold nanoparticles reported to synthesized gold nanoparticles by
was reported. In this method gold nanoparticles using different surfactants such as oleylamine, 1-
was reduced by the trisodium citrate which was octadecanethiol, poly (N-vinylpyrrolidone), and
combined with hydrogen tetrachloroaurate (III) AgNO3 in 1,5-pentanediol to stabilize the
tetrahydrate (chloroauric acid) and modified with colloidal solution. In this method gold
11-mercaptoundecanoic acid (MUA) by the self- nanoparticles were synthesized by the chemical
assembly monolayers (SAM) [6]. reduction of gold salt in organic solvent in the
presence of stabilizing agent [31].
The synthesis of gold nanoparticles via seeding
growth method has also been reported. Gold Another method for the preparation of gold
nanoparticles were grown from gold nanoparticles of size 30 nm was reported. In this
nanoparticles encapsulated in polyethylene method, a new class of block co-polymers were
glycol attached with dendrimers and have high used as template for the synthesis of stabilized
near infra-red absorption by using formaldehyde gold nanoparticles [6]. Modified burst method has
as a reducing agent [28]. Gold nanoparticles of been used for the synthesis of gold nanoparticles
size range 1.8 - 3.7 nm have been synthesized containing PEG of size 4 - 15 nm using a mixture
by using peptide-biphenyl hybrids (PBHs) which of HAuCl4 methanol and two thiol-PEG ligands
are good stabilizer for gold as capping agents via (PEG-550, PEG-2000) [7]. Well dispersed gold
single-phase system. Size of gold nanoparticles nanoparticles of size 6 nm have been
synthesized depends upon the structure and type synthesized by intra-molecular reduction of
of capping agent being used [17]. The reduction sodium gold sulfite Na3Au(SO3)2 [32]. Solution-
method has been used for the preparation of phase synthesis of gold nanoparticles having
dendrimers/Au nanoparticles. These particles size 13 nm by using cetyltrimethyl ammonium
were synthesized by the reduction of aqueous bromide (CTAB) as template or capping agent to
solution of HAuCl4 and dilute solution of avoid agglomeration has been reported.

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Recently, the synthesis of gold nanoparticles of Cissus quadrangularis (CQE) was used as
size 2 - 20 nm is proposed via the reduction of capping agent or reducing agent [37].
HAuCl4 with sodium borohydride by using
ethanol and isopropanol in the presence of tris(2- Green methods
aminoethyl) amine [33].
Green chemistry synthesis routes are
Physical methods environment friendly and non-toxic. A facile
green biosynthesis method for the preparation of
The -irradiation method was proved to be best gold nanoparticles of size 25 + 7 nm was
for the synthesis of gold nanoparticles with reported by using natural biomaterial egg shell
controllable size and high purity. The -irradiation membrane (ESM). In this method ESM was
method is adopted to synthesize gold immersed in aqueous solution of HAuCl4 without
nanoparticles with size 5 - 40 nm. In this method using any reductant [23]. Another green synthetic
natural polysaccharide alginate solution was approach was developed to synthesized gold
used as stabilizer [34]. Single step -irradiation sononanoparticles of size 5 - 17 nm by using
method has been adopted to synthesized gold high-power ultrasounds and sodium dehydrate
nanoparticles of size 2 - 7 nm by using bovine [19].
serum albumin protein as stabilizer [11]. Gold
nanoparticles are synthesized via photochemical Gold nanoparticles were successfully
synthetic approach. In this method, HAuCl4 and synthesized by adopting sun light irradiation
aqueous glycine solution was exposed to UV- method and were modified with folic acid and
irradiation. Basically amino acid capped gold capped by 6-mercaptopurine. In this method
nanoparticles were used as photochemical solar energy was used to reduce the gold salt
initiator which is then further functionalized with [16]. A new green chemistry method for the
glycine [12]. preparation of gold nanoparticles has been
reported, in which gold nanoparticles were
Microwave irradiation method was adopted to formed in aqueous NaCl solution from the bulk
synthesize gold nanoparticles by using citric acid gold substrate by natural chitosan without using
as a reducing agent and cetyltrimethyl any external stabilizer and reductant [38]. Gold
ammonium bromide (CTAB) as a binding agent nanoparticles of size 15 - 80 nm are also
[23]. Gold nanoparticles are synthesized by synthesized via another green synthetic route. In
adopting heating or photochemical reduction this method HAuCl4 was reduced by using citrus
method. Citrate, tartrate, and malate ligands fruits juice extracts [Citrus limon, Citrus reticulate
were used to reduce HAuCl4 [31]. Solvent free and Citrus sinensis] [39]. Edible mushroom was
photo chemical method is also used for the also used for the synthesis of gold nanoparticles
synthesis of gold nanoparticles supported on via sunlight exposure [40].
hydrotalcite, V-Al2O3 and TiO2 with size range of
20 - 140 nm directly in solid phase [32]. A new APPLICATIONS OF NANOPARTICLES
technique of photochemical method has been
reported for the preparation of gold-polyethylene Gold nanoparticles have unique electric and
glycol core-shell nanoparticles with size 10 - 50 magnetic properties due to their shape and size
nm in water by adopting redox and so they have been received great attention in
polymerization reactions. In this method gold salt research areas especially in the field of biological
was reduced by radical formation coated with tagging, chemical and biological sensing,
polyethylene glycol diacrylate by UV-process optoelectronics, photo thermal therapy,
with the help of photo-initiator 2-hydroxy-2- biomedical imaging, DNA labelling [1],
methyl-1-phenyl-1-propane [35]. Gold microscopy and photoacutisc imaging [3],
nanoparticles are also synthesized by using seed surface-enhanced Raman spectroscopy, tracking
approach. In this method 10 - 50 nm sized gold and drug delivery, catalysis [5] and cancer
particles were prepared by Co-60 irradiation by therapy [9] (Table 1).
using water soluble chitosan as reducing agent
[12]. Porous gold nanoparticles were synthesized Gold nanoparticles based sensors can detect
from alloys of silver and gold. In this method, first various metal ions by working on the principle of
of all micro-emulsion of nanoparticles were colour change due to the aggregation of gold
prepared by using precursors such as HAuCl4 nanoparticles. Such types of sensors have been
and AgNO3 and then reduced by NaBH4. After widely used for the detection of copper, mercury
that, de-alloying was done by nitric acid [36]. lead and arsenic in water [41].
Gold nanoparticles was prepared by microwave
irradiation method in which aqueous extracts of Noble metals such as gold nanoparticles play
key role in the synthesis of biosensors due to

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Table 1: Shapes of gold nanoparticles and their applications

Shape Size Application


Nano rod 2-5 nm Drug delivery and photothermal therapy [15].

Hollow particle 25 nm Photo-electronics, catalysis and cancer therapy [12]


Triangular particle 3.85-7.13 nm Highly effective against E. coli and K. pneumonia [23]
Faceted particle 50-100 nm Effective, reproducible, and stable large area substrates for NIR
SERS [near infra-red surface enhanced Raman spectroscopy] [25]
Nanocube 50 nm Field enhancement applications and refractive-index sensing [28]
Nanocage 50 nm Effective molecular contrast agent for nonlinear endomicroscopy
imaging [19] and in vivo medical applications [29]
Nanobelt Thickness, ~80 Strain sensors
nm, Width, ~ 20
m, Length,
~0.15 m.
Branched particle 90 nm Substrates for SERS-based imaging of kidney cells [30]

large surface area, small size, good also cause various side effects [11]. Cancer
biocompatibility, conductivity, and excellent patients undergoing radio and chemotherapy
catalytic properties. Nanoparticles combined with face drug resistance such as cisplatin, cancer
biomolecules have been used for the biosensing related fatigue (CRF) and several cardio vascular
applications such as combination of gold effects such as cardiomyopathy, ischemia,
nanoparticles and AuNPs/MPA arrhythmias, hyper tension, thromboembolism,
(mercaptopropionic acid) has been used in the pericardial diseases or heart attack as they
fabrication of biosensors which shows wide linear damage the cancer cells along with the
range between 0.25 mM and 1.25 mM glucose destruction of healthy cells [44].
concentration having detection limit of 0.025 mM
[42] (Figure 4). Most of the biosensors depend Besides of some conventional approaches,
on LSPR (localized surface plasmon resonance) chemotherapy remains the primary treatment for
of gold nanoparticles so in order to enhance the cancer but it is not much restorative because of
efficiency of biosensors gold nanoparticles have various side effects caused by unspecified drug
been immobilized in solid substrate [10]. distribution in the body due to several
Functionalized gold nanoparticles with calixarene chemotherapeutic agents such as cytotoxic
derivatives, crown ethers DNA and peptides [12] drugs [25]. Paclitaxel (PTX) shows cytotoxicity
have been used for the sensing applications against different types of cancer so it is
mainly for the recognition of amino acids, considered to be an essential chemotherapeutic
quaternary ammonium ions and pyridinium [13]. drug with limited therapeutic effects due to
Indium tin oxide electrode modified with gold toxicity caused by poor water solubility and
nanoparticles/TiO2 composites has been used for selectivity. Because of these shortcomings,
the estimation of catechol (CC) and effective approaches should be considered [28].
hydroquinone (HQ) with the help of voltametric Chemotherapeutic agents cause various side
method. Catechol has been successfully effects in cancer patients such as nephrotoxicity,
determined in tea sample by adopting this vomiting, myelosuppression, severe nausea,
method [35]. Another important application of ototoxicity and neurotoxicity due to CDDP
gold nanoparticles is in memory devices. Gold (cisplatin) administration whereas gastro
nanoparticles coated with suitable insulator intestinal disturbances, acute nausea, vomiting,
exhibit excellent stability for memory devices and stomatitis, alopecia baldness, neurologic
this insulation helps in prevention of disturbances, bone marrow, aplasia, cumulative
accumulation of charges when the applied field cardio toxicity and bone marrow depressant
has been removed [43]. effects due to doxorubicin administration [9].

COMMON DRUGS FOR CANCER Due to fluoropyrimidines (5FU), methotrexate,


THERAPY irinotecan and cisplatin patient may suffer from
adverse diarrhea and constipation [30]. When
Constructive pathways for clinical treatment of treated with temsirolimus as a single drug
cancer are confined. Surgical restriction, anemia, hyperglycemia, stomatitis,
chemotherapy and irradiation are some common hypophosphatemia, interstitial lung disease and
tactics used for cancer therapy but these pneumonia were reported in patients suffering
approaches are not only toxic, non-specific but from advanced renal cell carcinoma [31]. Each

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Table 2: Conventional intravenously administered drugs and their side effects

Chemotherapeutic
Cancer type Possible short-term side effect
agent
Carboplatin Cancers of the ovary, head Decrease in blood cell counts, hair loss (reversible),
(Paraplatin) and neck, and lungs confusion, nausea, vomiting, and/ordiarrhea
Decrease in blood cell counts, allergic reaction, including
a rash and/or labored breathing, nausea and vomiting that
Cisplatin (Platinol, Cancers of the bladder,
usually occurs for 24 hours or longer, ringing in ears and
Platinol-AQ) ovary, and testicles
hearing loss, fluctuations in blood electrolytes, and kidney
damage
Doxorubicin Breast cancer, lymphoma, Decrease in blood cell counts, mouth ulcers, hair loss
(Adriamycin) and multiplemyeloma (reversible), nausea and vomiting, and heart damage
Decrease in blood cell counts, allergic reaction, nausea
Cancers of the breast, and vomiting, loss of appetite, change in taste, thin or
Paclitaxel (Taxol)
ovary, and lung brittle hair, joint pain (short term), and numbness or
tingling in fingers or toes
Cancers of the colon,
Decrease in blood cell counts, diarrhea, mouth ulcers,
Fluorouracil (5-FU) breast, stomach, and head
photosensitivity, and dry skin
and neck

year, large numbers of deaths are caused by especially in drug delivery for cancer therapy.
cancer because lack of selectivity, drug targeting Gold nanoparticles followed three main pathways
ability, inefficient metastatic tumor therapy and for the cellular uptake which includes receptor-
drug resistant tumor cells (Table 2). Therefore mediated endocytosis, phagocytosis and fluid-
advanced chemotherapic treatments have been phase endocytosis [40].
needed to kill cancerous cells [32]. Today in
order to avoid side effects fuscous of scientists The toxicity of gold nanoparticles depends on the
are shifted towards natural products which still size, shape, synthesis method, surface charge,
needs to prove their effectiveness [45]. surface coating and functionalized molecules but
overall cytotoxicity of gold nanoparticles is in
GOLD NANOPARTICLE-MEDIATED acceptable level as gold nanoparticles are
DRUG DELIVERY considered to be non-toxic agents [44]. There are
two factors, i.e. drug release and transport, which
Targeted drug delivery is better than
are very important for the efficient drug delivery
conventional drug therapy because in targeted
system. Drugs are loaded on nanocarriers by
drug delivery drugs target the main effected area
noncovalent interaction or through covalent
and delivered drug locally so it minimize the side
conjugation with the help of pro-drug, which is
effects caused by conventional drugs [34].
treated by the cell. Gold nanoparticles have
Primary goal of developing anticancer agents is
functional flexibility due to their monolayers so
to minimize the various side effects caused by
they provide efficient system [45].
the conventional drugs and to improve selectivity
and efficiency of drug [35]. Targeted drug
ADVANTAGES OF GOLD
delivery is the main area of interest for scientists
NANOPARTICLES
recently and a lot of work has been done to
synthesized systems for targeted drug delivery Gold nanoparticles mediated drug delivery
such as nanoparticles, quantum dots, polymer systems have many advantages over other
gels, Fe3O4, and ZnO [18]. nanocarriers as well as to conventional drugs.
Gold nanoparticles have been widely used as
Gold nanoparticles have the ability of bio-imaging acancer antigen and in tumor therapies [15].
of the effected cancerous cells for therapy [13]. Some advantages are listed here; (i) Gold
For effective drug delivery system or drug nanoparticles have unique optical [16], physical
therapy it is important to investigate about the and chemical properties [7] due to their size and
biological effects of the nanoparticles [17] as gold shape [9]; (ii) Gold nanoparticles have high
nanoparticles have unique physical and chemical
surface area [17] which provide dense drug
properties and have strong binding attraction for
loading; (iii) These particles are biocompatible [1]
thiols, proteins [18], carboxylic acid [11]
and are readily available for conjugation with
aptamers [39] and disulfides so they have been small biomolecules such as proteins, enzymes,
extensively used in the field of biosciences carboxylic acid, DNA, and amino acids [2]; (iv)

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Gold nanoparticles have controlled dispersity [5]; 8. Lukianova-Hleb EY, Wagner DS, Brenner MK, Lapotko
(v) Due to small size and uniform dispersion they DO. Cell-specific transmembrane injection of
can easily reach to the targeted site with blood molecular cargo with gold nanoparticle-generated
flow [36]; (vi) They are non-cytotoxic to the transient plasmonic nanobubbles. Biomater 2012; 33:
normal cells [18]; and (vii) Gold nanoparticles are 5441-5450.
easily synthesized by various methods [22]. 9. Mishra A, Tripathy SK, Yun S-I. Fungus mediated
synthesis of gold nanoparticles and their conjugation
CONCLUSION with genomic DNA isolated from Escherichia coli and
Staphylococcus aureus. Process Biochem 2012; 47:
Gold nanoparticles have, in some ways, 701-711.
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wide spread applications in targeted drug potential application of PEGylated gold nanoparticles
delivery, imaging, diagnosis and therapeutics with size-dependent permeation through brain
due to their extremely small size, high surface microvasculature. Nanomed: Nanotechnol Biol Med
area, stability, non-cytotoxicity and tunable 2011; 7: 992-1000.
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