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0 Introduction

There has been a surge of interest in the understanding and application of the unique
chemical and physical properties of materials with sizes in the 1-100 nm size range, which
include individual structures such as clusters, nanoparticles, nanocrystals quantum dots,
nanowires, and nanotubes as well as the collection of these individual structures into two-
and three-dimensional assemblies.1 Nanomaterials, particularly nanoparticles, are too small
to act like bulk solid but too big to behave like atoms. Thus, they represent the transition
form between single atom or molecule and continuous bulk media and are therefore of
primary interest for basic research. Nanoparticles received a special attention to the world
of science because of their good potential for making new analytical tools for
biotechnology and life sciences. On the other hand, use of the anomalous properties of
nanoparticle provides a way for researchers to create new devices and technologies that
have a wide range of potential applications. In this study, the silver metal will be the focus
metal nanoparticles.

Silver is one of the oldest subjects of investigation in science and technology, its
regeneration leads to an increasing number of researches, especially to the world of
nanotechnology and nanobiotechnology. Silver nanoparticles, also known as silver colloids
are the most stable nanoparticles,2 since they display a wide variety of attractive aspects
because of their self-assembly, surface science, the growth behavior of the individual
particles, its size-related electronics, optical and magnetic properties, and their application
to biomedical engineering. It was estimated before that the highest commercialization of
nanoparticle was on Ag nanoparticles. Their application to the treatment of diseases is of
big importance since nanoparticles are able to target specific cells or organs. Recently, this
Ag colloid was used for food and clothing industry.3

As we all know, nanoparticles, especially the silver metal, has electrochemical and
optical sensors due to its small size and controllable dimension. In order to have a stable
nanoparticle, there are two certain requirements to have. First, the synthesis of nanoparticle
should be water dispersible in a concentrated aqueous media in order to obtain an extensive

conjugation to the desired molecule. Second, an efficient transfer of colloid to the media in
question is required in order to have a good assembly of the conjugates after the
nanoparticle is synthesized.

The present study will focus on silver nanoparticle attached to a biomolecule. Its
synthesis and characterization will be proposed in this paper. The application will also be
tackled and the importance of Ag nanoparticle functionalized with biomolecule will also be

2.0 Review of Related Literature
2.1 Synthesis of Metal Nanoparticles
2.1.1 Au Nanoparticles
Gold nanoparticles stabilized by thiol functionality are extraordinarily stable and
are therefore of a great system for studying nanostructure formation. These metal
nanoparticles have many applications, for example, as stains in biological systems. They
are also easy to synthesize, they have been intensively studies in recent years. A commonly
used synthetic method involves the reduction of a gold salt in the presence of capping agent
molecules such as thiols, citrates, or phosphines. The functionalities of these capping
agents can be altered to yield various chemical properties. 4
2.1.2 Cu Nanoparticles
Synthesis of well-dispersed Cu nanoparticles has been achieved by reduction of
aqueous copper chloride solution using NaBH4 in nonionic water-in-oil (w/o)
microemulsions formed by Triton X-100, n-hexanol, cyclohexane, and water.5 Rather than
producing copper oxide in aqueous solution, the experiment showed that metallic Cu
particles were formed without microemulsion because of the high local Cu concentration in
an aqueous pool of microemulsion. The absorption spectrum of the colloidal Cu particles
obtained in microemulsions does not exhibit the plasmon peak characteristics of the Cu
surface. It is conceivable that the lack of the plasmon absorption band is attributed to the
formation of a CuCl monolayer on the Cu nanoparticles.
2.1.3 Ni Nanoparticles
In the presence of SDS-PVP clusters, Ni nanoparticles are obtained by reduction of
nickel chloride with NaBH4.6 The interaction of nickel ions with sodium dodecyl sulfide-
PVP (SDS-PVP) clusters indicates the template function of the SDS-PVP clusters. From
the experiment, it shows that the dispersion and average size of spherical Ni nanoparticles
can be controlled by mediating the SDS-PVP clusters. The clusters the experiment were
studied via surface tension and UV-Vis spectrophotometry. The Ni ion associates onto the
headgroup of the SDS-PVP clusters by electrostatic interaction when the Ni nanoparticles
are formed from reduction. PVP was adsorbed onto the particle surface to prevent
agglomeration and the stabilization of the nanoparticles.

2.1.4 Fe Nanoparticles
Iron nanoparticles have been synthesized the by a one step thermohydrolysis of
nitrate iron (III) solutions. The microwave system was designed by the authors to be able to
induce very fast heating rates within an autoclave.7 The use f microwave oven is one fo the
methods researchers now use to synthesize nanoparticles due to its fast heating rate and
controllable heating power. Different nanoparticle sizes and shapes were prepared using the
2.2 Synthesis of Silver Nanoparticles
Use of direct laser irradiation has been reported for the fabrication of Ag
nanoparticle having a well-defined size and shape distribution in solution.8 In that study, Ag
nanoparticles were produced using an aqueous Ag salt solution and a surfactant in the
absence of a reducing agent.
A polyol-based process has also been used to synthesize spherical Ag nanoparticles
having various size distributions.9 Two variations of the process were used to investigate
the influence of reaction parameters such as temperatures and solvents on the resulting
nanoparticle size distribution. The first method was the heating method wherein a solution
containing Ag nitrate was heated to the reaction temperature. Here, the ramping rate was
determined to be a critical parameter affecting the particle size. The second method was the
injection rate method. Here, a silver nitrate aqueous solution was injected into hot ethylene
glycol. Rapid nucleation led to the production of the nanoparticles. The Ag nanoparticles
produced at an injection rate of 2.5 mL/s and a reaction temperature of 100 ºC have sizes
ranging from 15-20 nm. The injection rate and the reaction temperature were found to be
important factors in terms of reducing the particle size and attaining monodispersity for this
particular method.
PVP-coated Ag nanoparticles have been synthesized by the polyol method using
glycerine as both reducing agent and solvent.10 In this method, a metal precursor is
dissolved in a liquid polyol in the presence of a capping agent such as polyvinyl
pyrrolidone (PVP), which was completely dissolved at high temperature. PVP is a linear
polyer and stabilizes the nanoparticle surface via bonding with the pyrrolidone ring. The
polymer’s concentration was found to play an important role in determining the
nanoparticle size and shape.

Monodisperse samples of Ag nanocubes have been synthesized in large quantities
by reducing Ag nitrate with ethylene glycol in the presence of PVP. These cubes are single
crystals and are characterized by slightly truncated shape bounded by {100}, {110}, and
{111} facets.11 The presence of PVP and the molar ration of the PVP repeating unit to
AgNO3 were found to influence the geometric shape and size of the Ag nanoparticles.
Nearly cubic-shaped Ag nanoparticles have also been obtained by spin-coating colloidal
nanoparticles on a glass substrate.12
Another method that is widely used to synthesize Ag nanoparticles is through
solution-phase chemical reduction of metal salts. Typically, the metal precursors (AgNO3)
are dissolved in a solvent containing stabilizing reagents. The reducing agent, such as
borohydride, hydrogen, or citrate is added or generated in-situ in an aqueous solution of the
metal salt. In the case of non-aqueous systems, the reducing agent can also be the
stabilizing agent.13 In at least one case, the addition of NaCl solution to the Ag metal salt
solution has been shown to enhance the formation of nanoparticles.14
In addition to the studies of synthesizing Ag nanoparticle, another method of
synthesis had been done through the use of microwave oven. Microwaves have been used
to control the dimension of the Ag nanoparticles being produced. The main advantage of
using microwave for the preparation of Ag nanoparticle is the reaction rate, which
distinctly higher than in the case of conventional heating. In addition, microwave heating is
not only quick but also uniform. A polyol process that uses microwave has been
investigated for the synthesis of several nanophase metals uner different condition from
100 ºC to 200 ºC. The synthesis was carried out at 100 ºC and 150 ºC in the presence of
ethylene glycol, PVP, dodecyl amine, and oleic acid or trioctylphosphine to determine
whether particle size and shape can be controlled. The Ag nanoparticle size was controlled
using different capping agents. In addition, polychrome Ag nanoparticles have been
prepared by a soft solution approach under microwave irradiation using a solution of
AgNO3 in the presence of PVP without any reducing agent.15
The use of PVP has led to well defined Ag nanoparticle in the range of about 30-50
nm. Morphologically well-defined nanophase metals of Fe, Co, and Ni have been produced
in the presence of PVP and dodecyl amine, while the use of just PVP or PVP and
trioctylphosphine did no yield such particles. Moreover, Ag nanoparticle-sized cubes have

been synthesized via reduction of Ag nitrate using PVP as capping reatgents, a reagent used
to prevent reactive site from forming at the chain end of a molecule, may be used to
prevent agglomeration of nanoparticles.16 These results showed that a variety of well
defined nanophase metals can be produced using the microwave-polyol process in the
presence of a metal capping agent.17
The nature of the solvent turned out to be one of the determinants of nanoparticle
size and shape. For example, water, alcohols, DMF, and ethylene glycol have high
dielectric losses and high reduction ability. Therefore, they are ideal solvents for
microwave-induced nanoparticle synthesis. With microwave heating, the solvents and
reagents are able to react faster to form the desired Ag nanoparticles. Samples of single
crystalline polygonal plates, sheets, rods, wires, tubes, and dendrites have been prepared
within a few minutes under microwave heating.18
Changing various experimental parameters, such as the concentration of metallic
salt, surfactant polymer, chain length of the surfactant polymer, solvent, and reaction
temperature could control the morphologies and size of nanostructures. In general,
nanostructures with smaller sizes, narrower size distributions, and a higher degree of
crystallization have been obtained under microwave heating than those in conventional oil-
bath or water heating.
2.3 Other Nanoparticle Synthetic Methods
Nanoparticles have also been prepared using tip-directed scanning probe
microscopy techniques19 and deposition techniques onto nanotemplates.20 A double-pulse
electrochemical technique has been used to prepare Ag nanoparticles, the size, density, and
dispersity of the nanoparticles being sensitive to the pulse parameters.21 Nanoparticle
geometries such as triangles,22 nanoring,23 and nanoshells24 have also been synthesized
previously. In the case of composite nanoparticle, anatase TiO2 nanoparticles doped with
various dopants such as Nd3+, Pd2+, Pt4+, and Fe3+ have been synthesized using chemical
vapor deposition.25 TiO2 nanoparticles have also been prepared using techniques such as
impregnation,26 co-precipitation,27 sol-gel,28 and hydrothermal method.29

2.4 Silver nanoparticle Functionalized with Biomolecule
Attaching of Silver nanoparticle to phospholipids was made possible in an
experiment.30. The researchers aimed to develop a mechanism on how to attach the silver
nanoparticle to a phospholipid bilayer. The researchers were able to make simple two-step
approach to functionalize the silver nanoparticle with phospholipid bilayer by using the
presence of sulfur-hydrogen functionalities which also increased the free electron density
of the silver nanoparticle. It was shown in the UV-Vis and IR spectra that there is a strong
interaction between Ag-S which leads to the connection of the sulfur to the bilayer. In the
study, the researchers were able to propose a method to functionalize the nanoparticle with
biological molecules.

Another research on attaching a biomolecule onto the silver nanoparticle can be

found in the literature.31 The objective was to make a hybrid of Ag nanoparticle with
controlled sizes and be electrodeposited on a glassy carbon electrode via the reduction of
silver with the help of the DNA. The researchers were able to make the Ag nanoparticle-
DNA hybrid. The hybrid was able to demonstrate a good size distribution and a catalytic
ability to reduce H2O2 and dissolved oxygen, thus produce good sensitivity for rapid
detection of H2O2 in the absence of Oxygen. The researchers were also able to show that the
presence of DNA with the colloid reduced the aggregation of the nanoparticle. Based on the
good catalytic ability of the hybrid nanoparticles, the researchers were able to make a
biosensor with high sensitivity. The method done for the experiment was compared to other
electrochemical deposition methods. It showed that the proposed method is effective in
preparing well-dispersed nanoparticles with modified functional surface.

In addition to the studies mentioned above, another research about Ag colloids

functionalized with a biomolecule that is found to be pH dependent and was used to
monitor chemical activity of the biomolecule.32 The aim of the study was to attach 2-
aminothiophenol, a biomolecule to Ag nanoparticle. The authors had able to functionalized
the silver colloid and were able to demonstrate the pH sensing application of the
functionalized Ag nanoparticle based on the surface enhance Raman scattering. The pH
dependent molecule enabled the researchers to sense the pH over the range of 3.0 – 8.0.

The study also demonstrated that the nanoparticle can be used as a probe for delivering
chemical information from biological media and have also provided a new way to monitor
chemical transformation at the cellular level.

In addition to the studies about coupling of Ag nanoparticle with a biomolecule,

another study was done about the attaching of biological enzyme with a nanoparticle. 33 The
authors’ objective on this study was to amplify the signal of electrochemical DNA based on
the biocatalytic deposition of silver nanoparticles and silver enhancement methods. The
coupling of the biological enzyme and the Ag nanoparticle makes the immunoassay
ultrasensitive, which is more favored compared to other metal nanoparticles. It was shown
in the research that once a Ag nanoparticle binds with a biological molecule, this biological
molecule will have a great electrochemical properties that is amplified from the molecule.
The approach of the researchers also showed that the strategy of the proposed study was to
achieve lower detection limit for bioassays.

2.5 Silver nanoparticle Coupled with Polymers

Strong resonant coupling with light and plasmons of Ag nanoparticle lead to huge
number of amazing and technologically important optical effects, one of resonant coupling
with light and plasmons is the enhancement of fluorescence from a nearby molecule.

A research about Ag nanoparticle attached to a polymer using metal-enhanced

fluorescence technology.34 The researchers’ objective is to produce a method to synthesize
silver-deposited polycarbonate film based on fluorescence detection with enhanced
sensitivity. In the study, polycarbonate was chosen as the polymer of interest due to its
widespread use in biotechnology. The researchers were able to deposit the Ag nanoparticle
to the polymer using UV radiation. The researchers used polycarbonate polymer instead of
glass substrates for metal-enhanced fluorescence technology since polycarbonate films are
suitable and cheap.

Another report about Ag nanoparticle coupled deposited in a polymer. According to

the study, polyaniline is one of the most conducting polymers because of its potential

application such as batteries, electrochromic devices, chemical sensors, and biosensors.35
The authors’ objective in the study was to prepare and characterize oligoaniline derivative
nanofiber containing silver nanoparticles. In the experiment polyvinylpyrrolidone (PVP)
was used to immobilize the nanoparticle and the polymers as the reducing agent for Ag+ in
the PVP solution. Using electrospinning technique the said silver nanoparticle with
polymer was synthesized by the researchers. The morphology of the hybridized
nanocomposites and the distribution of Ag nanoparticles were characterized by scanning
electron microscope and transmission electron microscope.

2.5 Interaction of Ag Nanoparticles with Diseases

The interaction of metal nanoparticles, specifically silver, with biomolecules and
microorganisms is a growing field of study. Many areas of research have exploring the
possibilities of Ag nanoparticles curing or inhibiting some diseases.

A res36earch about Ag colloids inhibiting HIV-1 and therefore causing the cell to
commit apoptosis. The authors’ aim on this study was to bind the Ag nanoparticles with the
HIV-1 so the virus will be inhibited and therefore lead to apoptosis. The researchers were
able to synthesize a silver nanoparticle with the size ranging from 1-10 nm. The
synthesized colloid was bound to the virus through the attachment of gp120 glycoprotein
knobs. The exposed sulfur-bearing residues of the glycoprotein knob of the virus make it an
attractive site to the Ag nanoparticles. The authors have shown that the interaction of Ag
nanoparticles with HIV-1 is really possible and were able to demonstrate that once the
colloids were attached to the virus, the silver nanoparticle inhibits the virus from attaching
to the host cells.

Due to silver’s antiseptic properties to several bacteria, including the famous E.

coli, another study about Ag nanoparticle interacting with microorganisms.37 The objective
was to synthesize a cheap and environmental friendly Ag nanoparticle that has the ability to
kill bacteria. The researchers of the project were able to synthesize Ag nanoparticle through
oxidation technique. After the nanoparticle was produced the researchers incubated E. coli
bacteria overnight on a plain glass slide coated with silver nanoparticle and on a glass slide

without the silver nanoparticle. The authors found out that all the bacteria were killed on
the glass with the silver nanoparticles and the bacteria without the colloids increased in
number. As a result, the authors confirmed that the nanoparticles are toxic to bacteria. The
authors have demonstrated that Ag nanoparticles interacted with the outer membrane,
causing structural changes which lead to structural degradation of the microorganism and
eventually apoptosis of the cell of the bacteria.

In addition to the studies mentioned about the interaction of silver nanoparticle with
microorganisms, another study of the silver colloid as an antimicrobial agent.38 The purpose
of the study was to show the antimicrobial activity of silver nanoparticle. The silver
nanoparticle’s unique chemical and physical properties were used in the experiment as an
alternative for the development of new antimicrobial agent. It was shown that once the Ag
nanoparticle contacted with the moisture, the silver gets ionized. The researchers have
shown that the silver ion binds to tissue proteins and brings structural changes in the
bacterial cell wall and nuclear membrane which will lead to cell distortion and death. They
have also shown that the silver ion binds to bacterial DNA and RNA by denaturing and
stops bacterial multiplication. The researchers proposed a possible mechanism of silver that
seems to kill all the bacteria it gets contact with. The silver nanoparticles or the silver ions
interact with the thiol group compounds found in the respiratory system of the bacteria.
Then silver binds with the cell wall and membrane and inhibits the respiration process
which again leads to cell death of the bacteria.

However, despite the fact that Ag nanoparticles have many uses in the environment
such as antimicrobial agent, biosensors, and virus killers, it was reported that Ag
nanoparticles can damage DNA in mammalian cells.39 The authors’ objective in this study
was to examine the DNA damage response once the cell is exposed to silver nanoparticle.
The authors of this research expose the DNA of mouse embryonic stem cells and fibroblast
to polysaccharide surface functionalized and non-functionalized Ag nanoparticle. In the
article, p53 was introduced as the master guardian of the cell and is able to activate cell
cycle checkpoints, DNA repair, and cell death response to maintain genomic stability. It
was shown that both types of silver nanoparticles mentioned earlier normalized the cell

cycle checkpoint p53. It was shown that in the absence of cell stress of DNA, p53
concentration was low but in the presence of the silver nanoparticle, the concentration of
p53 became high. Therefore, the expression of p53 protein in two types of mammalian cells
by Ag nanoparticles exposure suggested that p53 protein could be a molecule marker to
assess the genetic nanotoxicity. The observation of the researchers also suggested that the
different surface chemistry of silver nanoparticles induced different damage to DNA, the
coated silver colloid showed more severe damage that the uncoated Ag nanoparticle. The
observations also showed that polysaccharide functionalized nanoparticle are much
distributed compared to the non - functionalized Ag nanoparticle since agglomeration
happens and limits the surface area distribution and also limits the access of the particle to
membrane bound organelles.

2.6 Ag Nanoparticle Used as Biosensors to Biomolecules

During the recent years, scientific interest has been raised by the discovery of
different nanoparticles. One of these nanoparticles is the Ag nanoparticles due to its good
conduction of electricity and its ion can easily combine with many biological compounds
through electrovalent bond or coordinate bond. Ag nanoparticle can be also easily absorbed
in an electrode which turns to easily catalyze reduction – oxidation processes. This certain
kind of property of silver makes it a good biosensor for biological molecules.

A research on Ag nanoparticle was used as biosensor for cysteine. 40 The objective of

the research was to study the electrochemical behavior of Ag nanoparticle functionalized
with mercury film glassy carbon electrode. The functionalized nanoparticle on this research
was devised as a biosensor to study the catalytic activity of the electrochemical response of
cysteine, an amino acid which exhibits irreversible oxidation and requires positive
overpotential to most electrode surfaces for the electrochemical detection activity of the
molecule. In the study, a silver nanoparticle was synthesized according to literatures. The
mercury film electrode was dipped into the prepared silver colloid for 2 days at room
temperature to make the doped electrodes. The constructed electrode in the study was
dipped into an acetated buffer solution containing certain concentration of cysteine. It was
demonstrated that the cysteine molecule was absorbed since the size of the electrode

increased in diameter. To test the electrochemical response of cysteine, the mercury film
glassy carbon electrode without the Ag nanoparticle was made and dipped into the cysteine
solution. It shows that using cyclic voltameter the one without the Ag colloid gives low
redox peaks. In contrast with the one with Ag nanoparticle electrode, it showed a pair of
reversible and more sensitive redox peaks, which also shows the reduction and oxidation
peaks have the same height. The behavior of the peaks showed that Ag nanoparticle doped
in mercury film could catalyze the electrochemical reaction of cysteine. The authors have
demonstrated that when silver nanoparticles are attached to an electrode it can best work
for the determination of electrochemical activity of biomolecules and therefore can act as a
new biosensor.

Another research about Ag colloid used as biosensor for DNA using

electrochemical detection was found.41 The objective of the study was to develop an
electrochemical detection method for biological assay for detecting DNA hybridization
based on the precipitation of silver onto gold nanoparticle DNA labels. For the
electrochemical detection of DNA hybridization based, the added silver nanopraticles with
the gold nanoparticle label on it enhances the properties of the gold metal. One of the facts
of this research was on gene analysis and mutant detection. The authors of the study
demonstrated that when a silver-enhanced colloidal gold is used the sensitivity of the
biosensor increased by about two orders of magnitude compared with the one with out the
silver when differential pulse voltammetry was used to measure the signal of the DNA

To add to the studies about Ag nanoparticle used as a biosensor, another report on

Ag nanoparticle used to improve a biosensor to detect glucose. 42 The objective of the study
was to use Ag nanoparticle to enhance the sensitivity of the glucose biosensors based on the
immobilization of glucose oxidase. The glucose oxidase was mixed with the silver colloid
and coated onto a platinum electrode with polyvinyl butyral (PVB) and glutaraldehyde by
sol-gel process. The researchers studied the effect of Ag nanoparticle on the sensitivity
response of glucose biosensor by electron micrograph. Two media were prepared, one with
Ag nanoparticles and one without. The other parameter that was used in the experiment

was to employ a hydrophobic and hydrophilic Ag nanoparticle onto to the glucose
biosensor. The authors showed that response of the electrode containing Ag colloid
increased compared to the one without. The results showed that the response of the
electrode containing the hydrophobic Ag nanoparticle was much greater compared to the
electrode containing the hydrophilic Ag nanoparticles. The authors also demonstrated that
Ag nanoparticle functioned as an electron-conducting pathway between the prosthetic
groups and the electrode surface, thus the electron transfer rate between glucose oxidase
and the electrode increased significantly.

3.0 Proposal

Cancer detection and treatment has been the interest of most of the researchers due

to its fast rate of proliferation in the human body. The inherent difficulty of isolating cancer

cells due to its almost similar structure to human cell has been the challenge for researchers

in this field. The application of the drugs and as much as radioactive compounds post the

problem of selectivity of the action on cellular destruction of the cancer cells. Other

chemical compounds also are non selective in their action thus creating variety of side

effects. However, the fast and emerging field of materials science opens vast possibilities of

manipulating materials that could have beneficial medical applications. Particularly,

nanotechnology has been found to have more than just electronics application but instead a

very useful tool in the medical science and on the treatment and management of diseases.

Aside from the direct application of nanoparticles in disease treatment such as

antimicrobial properties of metal nanoparticles. Other novel techniques are introduced to

even diversify the applications of these materials. New materials find its application from

optics, to magnetic as far as sonics.

This study exploits the possibilities that these disciplines could offer in the design

of a new material that will improve the diagnosis, treatment and management of certain

cancer diseases.

With the advent of medical physics, the applications of the magnetic properties of

matter allowed the development of magnetic resonance imaging technology which then

improves the visual diagnosis of the patient’s disease. Here we propose the use of

magnetite as a binding molecule that will allow the detection and attachment of the

nanoparticle in the cancer cell. However, the inherent difficulty of allowing the magnetite

to increase its retention time in the human system and maintaining selectivity is an issue

that needs to be addressed. The group proposes the incorporation of the magnetite in a

hydrophilic polymer such as polyethylene glycol to allow increase in circulation of the

magnetite in the system to allow exploration of to most part of the human body. This will

thus be the composition of a fraction of what the surface of the nano particle would be

made of.

It is also a concern of the group that surface poisoning would eventually hinder the

molecule of even reaching the site of binding interest. It is then proposed that the surface of

the magnetite be then encapsulated with silver shell which will protect the active sites of

the magnetite from ions and proteins that might bind with it. The preparation of the

magnetite is described.43 Other studies describe that the most efficient means of

synthesizing magnetic nano particles/crystals is by reverse micelle process.44,45 More recent

research however describes a modified micellar means of synthesizing the nanoparticle

with functional groups attached to it.46 For the purpose of this study, we shall use rather the

reverse micelle process.

3.1 Synthesis of the magnetite nanocarrier of drug

Optimal size and distribution of nanoscale magnetite is made possible to be

synthesized in a nanoreactor.47,48,49,50 This method employs two separate microemulsion

preparations. The first microemulsion involves oil base which is comprise of isooctane and

uses a surfactant of diiso-octylsulphoccinate (AOT). This microemulsion specifically

contains 2 mL 30% NH4OH + 2.4 mL water, + 66 mL 0.50 M AOT isooctane. The second

type of microemulsion is composed of 0.576 g FeSO4*7H2O made to dissolve in 8 mL H2O

and 66 mL AOT isooctane. Both systems were sonicated for 10 minutes. The two

emulsions were stirred mechanically for a period of 75 minutes at temperature of 50 oC.

The first system uses NH4OH as precipitating agent. The precipitation of Fe3O4 is shown by

the following:

3FeSO4 * 7H2O + 6NH4OH + ½O2  Fe3O4 + 3(NH4)2SO4 + 24H2P

The resulting mixture is then treated with methanol to allow separation of

surfactant. The resulting solid is then washed with methanol-acetone-water, which was then

dried over an oven for 30 minutes at 90 0C.

3.2 Surface Functionalization of Magnetite

Surface functionalization modifies the hydrophobic nature of the magnetite making

it more susceptible for drug conjugation. Bifunctional methyl 3-mercaptoproprionate

(HSCH2CH2COOCH3) attaches itself with the magnetite thru the Fe-S bond. Another

inherent problem is how to attach the magnetic nanoparticle with the anti-cancer drug. Or

make the drug acceptable for attachment with the nanoparticle. This is made possible by

changing the –OCH3 to –NHNH2 via hydrazinolysis since –NHNH2 conjugates with the

antitumor drug, doxorubicin. These hydrazones are found to be stable at relatively neutral

environment such as pH 7.00. However, the hydrazone link at pH relatively around 5.00-

5.50, which is a similar pH in the endosomes/lysosomes of cancer cells, hydrolyzes thus

releasing the active pharmaceutical ingredient doxorubicin.51,52 The said antitumor drug

conjugates to the surface of the functional groups of the magnetite by linking the hydrazone

to the carboxyl group of doxorubicin.

There have been other drug delivery techniques reported which utilizes polymers

which encapsulates the nano crystal/particle where upon exposure to high temperature will

cause its decomposition thus releasing the anti-cancer drug.53 This study however,

introduces the use of silver nanoparticle as coating material as a means of protecting the

magnetite and doxorubicin from premature reaction and poisoning.

It is then suggested that the encapsulation of the functionalized magnetite by silver

nanoparticle be done adopting the method already reported for coating individual magnetite

with silver nanoparticle.54

3.3 (Fe3O4)core–Agshell Nanoparticles

Each of the Fe3O4 particles are coated separately by the metal silver to preserve the

magnetic property of the particle for a considerable amount of time. This is done by silver

sulphate was added with Fe3O4 in a molar ratio of 0.5:1 in a 0.5 g of glucose. These were

then sonicated for 15 minutes and then heated with stirring over a water bath for an hour.

The completeness of the reaction is qualitatively detected by the browning of the originally

black iron oxide. The particles were then centrifugated and separated from the clear


Upon diffusion in the human body, the drug delivery device (DDD) enters the

cancer cell. The conditions inside the cancer cell activate the release of doxorubicin making

the release to be highly specific. The location of the tumor cells are located by the use of

magnetic resonance imaging. Upon locating nano optics will irradiate the site to which

most of the DDD are concentrating. Laser desorption/ionization of Ag is capable of

producing both positively and negatively charged silver clusters up to 100-mer.55 A pulsed

nitrogen laser capable of producing a wavelength of 337 nm for MALDI and TOF using a

delayed-extraction mode was used. The application of laser on magnetite coated with silver

nanoparticle will desorbed the silver by ionising the silver particles. The desorpted silver is

expected to be chelated by the carboxyl group and by the azide group. Making the silver

cation still attached to the DDD. The deprotected magnetite will then attach itself to the

tumour cells. Magnetic agitation of the magnetite will create sufficient amount of thermal

energy that would even augment destruction of the cancer cells.56 It is even explored the

possibility of mobilizing and concentrating to a particular site the tumour cells with the

aide of a magnet making the intervention of removing the cancer cell debris less invasive

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