1

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GROUP MEMBERS:
NAME

NUR ADIBAH BINTI ADNAN 2014690162

QUESTION
MARKS
SAZLIN
IMAZ
BINTI
Abstract
/3 MOHD ISMAIL - 2014409528
Research background
/10
AINUL MARDHIAH BINTI ABDUL RAHIM 2014437822
Characterization
/10
Application
/4
FACULTY
: CHEMICAL ENGINEERING
FACULTY (FKK)
References
/3
PROGRAM
: EH220
Total
/30
GROUP
CODE & COURSE
TOPIC
LECTURES NAME

: EH2201A
: CHE434 / PROCESS CHEMISTRY
: ASSIGNMENT 2
: DR. NURUL FADHILAH BINTI KAMALUL ARIPIN

DATE OF SUBMISSION : 19/12/2014

MARKS

1.1 Abstract
The development of novel nanomaterials and their use in biomedicine has received much
attention in recent years. Significant advances have been made in the synthesis of
nanomaterials with controlled geometry, physicochemical properties, surface charge, and
surface tailoring with bioactive polymers. These successful efforts have resulted in improved
biocompatibility and active targeting of tumour tissues, leading to the development of a
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diverse range of nanomaterials that can recognize cancers, deliver anticancer drugs and
destroy tumours by a variety of therapeutic techniques. The focus of this review is to provide
an overview of the nanomaterials that have been devised for the detection and treatment of
various types of cancer, as well as to underline the emerging possibilities of nanomaterials for
applications in anticancer therapy.In the present study,there are the ability of Titanium Dioxide
nanoparticles to act as a drug carrier for loading doxorubicin.It also bonds with an antibody
and attaches itself to cancer cells.This nanobio technology may eventually provide an
alternative form of therapy that targets only cancer cells and does not affect normal living
tissues.Titanium Dioxide is a versatile photoreactive nanomaterial that can bonded with
biomolecules.Under this study also the characterization method used consists of Atomic force
microscopy and Transmission electron microscopy in study of cancer cells.However in the
side of application for this study of nanomaterial in treating cancer cells is drug carrier role of
Titanium Dioxide nanoparticle and the second application is a targeted cancer treatment using
Titanium Dioxide nanomaterials.

1.2 Background Studies

Titanium dioxide
Titanium (Ti), the ninth most bountiful element in the earth's crust and having the average
concentration in the earth's crust is 4400 mg/kg. Due to its tendency for oxygen and other
element, Ti does not exist in the metallic state. The most common oxidation state of Ti is +4,
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but +3 and +2 states also exist. Metallic Ti, TiO 2, and TiCl4 are the compounds most widely
used in industry. TiO2 (CAS-No. 13463-67-7), also known as titanium (IV) oxide, titanic acid
anhydride, titania, titanic anhydride, or Ti white, is the naturally occurring oxide of Ti. TiO 2 is a
white non-flammable and odourless powder with a molecular weight of 79.9 g/mol, boiling
point of 2972C, melting point of 1843C, and relative density of 4.26 g/cm3 at 25C. TiO 2 is a
poorly soluble particulate that has been widely used as a white pigment.
Titanium dioxide has two crystal structures that is anatase and rutile, with anatase being more
chemically reactive. Indeed, anatase generates ROS when irradiated by UV light. It has been
suggested that TiO2 anatase has a greater toxic potential than TiO 2 rutile. However, anatasegenerated ROS does not occur under ambient light conditions. TiO 2 NPs are normally a
mixture of anatase and rutile crystal forms. The principal parameters of particles affecting their
physicochemical properties include shape, size, surface characteristics and inner structure.
TiO2 FPs (the rutile form) is believed to be chemically inert. However, when the particles
become progressively smaller, their surface areas, in turn, become progressively larger, and
researchers have also expressed concerns about the harmful effects of TiO 2 NPs on human
health associated with the decreased size. Surface modification such as coating, influences
the activity of TiO2 NPs. [1]
Titanium dioxide (TiO2) nanoparticles can act as photosenitizer which is a known photo
catalyst and reacts with water to produce oxidizing free radicals when exposed to UV light,
which can result in localized damage to nearby cells. Recent in vitro studies on glioma cells
have demonstrated the potential of such nanoparticles for photodynamic therapy. A similar
effect has recently been produced in TiO2 nanoparticles with ultrasonic stimulation, which is
able to kill nanoparticle-impregnated glioma cells when exposed to ultrasound in a similar
manner to UV-stimulated nanoparticles. TiO2 nanoparticles are also essentially non-toxic and
hence show considerable promise as cancer therapy agents. [2]

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synthesis of
titanium
dioxide
gas phase
method

Solution route

precipitation

CVD

solvothermal

PVD

electrochemic
al

SPD

combustion

other method

microemulsio
n

sol-gel

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Solution route
The most preferred for the synthesis of nanostructured titanium dioxide for, especially the
synthesis of thin films. The benefit of this method is the ability to control over the
stoichiometry, producing homogeneous materials, allowing formation of complex shapes, and
preparation of composite materials. However, it might need expensive precursors, long
processing times, and the presence of carbon as an impurity.

Precipitation Method
These involve precipitation of hydroxides by the addition of a basic solution (NaOH, NH 4OH
and urea) to a raw material followed by calcination to crystallize the oxide. It usually produces
anatase even though sulphate or chloride is used. In particular conditions, rutile may be
obtained at room temperature. The disadvantage is the tedious control of particle size and
size distribution, as fast (uncontrolled) precipitation often causes formation of larger particles
instead of nanoparticles as raw materials, TiCl3 or TiCl4 are mainly used.

Solvothermal Method
These methods employ chemical reactions in aqueous (hydrothermal method) or organic
media (solvothermal method) such as methanol, 1,4 butanol, toluene under self-produced
pressures at low temperatures (usually under 250 0C). The solvothermal treatment could be
useful to control grain size, particle morphology, crystalline phase, and surface chemistry by
regulating the solution composition, reaction temperature, pressure, solvent properties,
additives, and ageing time. As sources of Titanium dioxide, in hydrothermal synthesis,

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TiOSO4, H2TiO(C2O4)2, H2Ti4O9.0.25 H2O, TiCl4 in acidic solution, and Ti powder are reported
as examples.

Hydrothermal Method
Hydrothermal synthesis is normally conducted in autoclaves with or without Teflon liners
under controlled temperature and/or pressure with the reaction in aqueous solutions. The
temperature can be elevated above the boiling point of water, reaching the pressure of vapour
saturation.
Titanium dioxide nanoparticles can be obtained by hydrothermal treatment of peptized
precipitates of a titanium precursor with water. The precipitates were prepared by using
solution of isopropanol and titanium butoxide into deionized water, and then they were
peptized at 70 C for 1 hour in the presence of tetraalkylammonium hydroxides (peptizer).
After filtration and heat treatment, powder of Titanium dioxide nanoparticles was obtained.
Titanium dioxide nanoparticles mainly with anatase phase were synthesized by using titanium
alkoxide, added drop wise to a mixed ethanol and water solution at pH 0.7 with nitric acid, and
reacted at 240 C for 4 hour. Titanium dioxide nanorods have also been synthesized with the
hydrothermal method. Zhang et al. obtained titanium dioxide nanorods by treating a dilute
TiCl4 solution at 333-423 K for 12 hour in the presence of acid or inorganic salts. A film of
titanium dioxide nanorods deposited on a glass wafer was reported by Feng et al. using
titanium trichloride aquous solution supersaturated with NaCl.
Titanium dioxide nanowires are obtained by treating titanium dioxide white powders in a 10-15
M NaOH aqueous solution at 150-200 C for 24-72 hour without stirring within an autoclave.
Briefly, titanium dioxide powders are put into a 2.5-20 M NaOH aqueous solution and held at
20-110 C for 20 hours in an autoclave. Titanium dioxide nanotubes are obtained after the
products were washed with a dilute HCl aqueous solution and distilled water.

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Solgel Method
Sol-gel methods are used for the synthesis of powders, membranes, and thin films of
Titanium dioxide nanoparticles, nanotubes, nanobelts etc. The solgel method has many
advantages such as purity, homogeneity, ease and flexibility in introducing dopants in large
concentrations, stoichiometry control, control over the composition, and the ability to coat
large and complex areas compared to other fabrication techniques. In a typical sol-gel
process, a colloidal suspension, or a sol, is formed from the hydrolysis and polymerization
reactions of the precursors, which are usually inorganic metal salts or metal organic
compounds such as metal alkoxides. Complete polymerization and loss of solvent leads to
the transition from the liquid sol into a solid gel phase. Sol-gel method is mainly divided into
two routes, namely non-alkoxide and the alkoxide. The non-alkoxide route uses inorganic
salts (such as nitrates, chlorides, acetates, carbonates, acetylacetonates, etc.), which
requires an additional removal of the inorganic anion, while the alkoxide route uses metal
alkoxides as starting material. In alkoxide route a sol or gel of titanium dioxide is obtained by
hydrolysis and condensation of titanium alkoxides. As titanium sources, titanium-tetraethoxide, titanium-tetraisopropaxide, and titanium-tetra-butoxide are most commonly used
alkoxides.

Micro emulsion method

Water in oil micro emulsion has been successfully utilized for the synthesis of nanoparticles.
Micro emulsions may be defined as thermodynamically stable, optically isotopic solutions of
two immiscible liquids consisting of micro domains of one or both stabilized by an interfacial
film of surfactant. The surfactant molecule generally has a polar (hydrophilic) head and a
long-chained aliphatic (hydrophobic) tail. Such molecules optimize their interactions by
residing at the two-liquid interface, thereby considerably reducing the interfacial tension. In
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particular, hydrolysis of titanium alkoxides in micro emulsions based on solgel methods has
yielded uncontrolled aggregation and flocculation except at very low concentrations.
Combustion synthesis
Combustion synthesis (hyperbolic reaction) leads to highly crystalline fine/large area particles.
The synthetic process involves a rapid heating of a solution/compound containing redox
mixtures/redox groups. During combustion, the temperature reaches about 650 0C for a short
period of time (12 min) making the material crystalline. Since the time is so short, particle
growth of Titanium dioxide and phase transition to rutile is avoided.

Electrochemical synthesis
Electrochemical synthesis may be used to prepare advanced thin films such as epitaxial,
superlattice, quantum dot and nanoporous ones. Also, controlling electrolysis parameters like
potential, current density, temperature and pH can easily control the characteristic states of
the films. Eventhough, electro deposition of titanium dioxide films by various Ti compounds
such as TiCl3, TiO(SO4), and (NH4)2TiO(C2O4)2 is reported, use of titanium inorganic salts in
aqueous solutions is always accompanied by hinder, due to the high tendency of the salts to
hydrolyze. Also, to that nanoporous titanium dioxide thin films have been synthesized
anodization of titanium sheet in aqueous solution of fluorine containing compound.

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Gas phase methods

Used for the preparation of thin films. These methods can involve chemical or physical
reaction. Powders can also be synthesized by this method.

Chemical vapor deposition (CVD)

Chemical Vapor Deposition is a widely used versatile technique to coat large surface areas in
a short span of time. The family of CVD is extensive and split out according to differences in
activation method, pressure, and precursors. Compounds, ranging from metals to composite
oxides, are formed from a chemical reaction or decomposition of a precursor in the gas
phase.

Physical Vapor deposition (PVD)

Physical Vapor Deposition is another class of thin-film gas phase deposition techniques in
which precursor and product do not go under chemical changes because of the stability of
gas phase. The most commonly employed PVD technique is thermal evaporation. PVD is a
so-called line-of sight technique, example; the gaseous stream of material follows a straight
line from source to substrate. This leads to shadow effects that does not present in CVD. In
electron beam (Ebeam) evaporation, a focused beam of electrons heats the selected
material. These electrons in turn are thermally generated from a tungsten wire that is heated
by current. Titanium dioxide films, deposited with E-beam evaporation, have superior
characteristics over CVD grown films where smoothness, conductivity, presence of
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contaminations, and crystallinity are concerned, but on the other hand, production is slower
and more laborious.

Spray pyrolysis deposition (SPD)

SPD is a type of CVD in which aerosol deposition technique is used for the synthesis of
nanostructured titanium dioxide thin films and powders. There are several small derivatives of
this technique, mainly differing in the formation step of the aerosol and the character of the
reaction at the substrate (gas-to-particle synthesis and droplet-to-particle synthesis). It has
been used for preparation of (mixed) oxide powders/films and uses mostly metal-organic
compounds or metal salts as precursors. The size of the particles formed and the morphology
of the resulting film are strongly dependent on deposition parameters like substrate
temperature, composition and concentration of the precursor, gas flow, and substratenozzle
distance. Some of these parameters are mutually dependent on each other.

Other methods
Sputtering (either using direct current (DC) or radio frequency (RF) currents) is used quite
frequently to produce titanium dioxide films. Molecular beam epitaxy is a technique that uses
a (pulsed) laser to ablate parts of a titanium dioxide ceramic target. The material is deposited
on the substrate in an argon/oxygen atmosphere or plasma. Ion implantation is seldom used
to synthesize titanium dioxide and is based on the transformation of precursor plasma to
titanium dioxide, which only becomes crystalline after an annealing step. It is, however,
frequently used to implant ions in titanium dioxide films (doping) to improve the photo catalytic
activity. Another unusual technique is dynamic ion beam mixing, which uses high-energy O 2+
and/or O+ beams and Ti vapour to deposit titanium dioxide films with high speed and control
over the composition. Sonochemical is another method in which ultrasound waves are used
for the formation of nanostructured titanium dioxide. Microwave method is also used for the
synthesis of Titanium dioxide nanomaterials. [3]
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1.3 Characterization
Atomic force microscopy:
Atomic force microscopy or AFM is a relatively novel method. It was invented in 1986, the first
new extension of scanning probe microscopy. Its technique is based on detection of forces
acting between a sharp probe, known as AFM tip, and the samples surface. A very flexible
cantilever attached to the tip. The various methods detected any motion of the cantilever.
Laser light is reflected from the cantilever. The tip is brought to contact or near-contact with
the surface of interest.
Scanning over the surface, AFM system records the deflection of the cantilever, due to very
small forces between the atoms of the probe and the surface, with sub-nanometer precision.
The only difference is the presence in AFM of a very sensitive detection system,
microscopically sharp tips, and extremely high-precision tip sample positioning. The deflection
signal (or any derivations of the deflection) is recorded digitally, and can be visualized on a
computer in real-time.

Photo Detector

Laser source

AFM cantilever
scanning

Sample surface
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Figure 1.1 schematic view of the AFM method

Modes of AFM Operation:

Contact Mode
In contact mode, AFM tip is in actual contact with the samples surface. In principle, AFM in
this mode can work precisely as described above. However, if there is a bump on the surface,
the cantilever will be deflected more, and consequently, AFM tip scans over the surface with
more force. When the tip comes across a bump on the surface, the deflection of the cantilever
increases, and the feedback system elevates the whole cantilever holder so that the
cantilevers deflection is adjusted back to its original value, and the cantilever is returned to its
original position. In the case, the same feedback system moves the cantilever down to again,
maintain the same deflection. This provides the same so-called load force between the tip
and the sample.

Pros of contact mode:

This is the simplest mode of operation. It requires minimum operational skill and basic
hardware.
Allows very fast scanning (typically 0.10.5 second per scan line).
The load force can be controlled.
Good signal to noise ratio even in a noisy environment.
Cheaper and more robust cantilevers can be used.

Cons of contact mode:

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The tip can stretch or even scratch the surface. This will lead to artifacts, therefore
disrupting the sample and leading to images and measurements that are not
representational of the original sample.
The tip can remove poorly attached parts of the sample. Apart from just damaging the
surface, this can contaminate the tip surface and prevent it from being used any
further.
Can provide only limited information about the surface. Contact mode is the best on
solid and well-fixed surfaces. It normally requires rather soft cantilevers (spring
constant (a characteristic measure) in the range of 0.0011 Nm1).

Tapping/AC/Intermittent Contact Mode

To further minimize the tip impact onto the surface, dynamicor intermittent contact mode, also
commonly known as Tapping mode was introduced. Another name use for this mode is AC
mode. In this mode the tip taps, or oscillates up and down very fast, touching the sample
surface for a very short period of time during relatively slow lateral scanning. This
considerably decreases scratching (although it does not eliminate it completely). While in
contact mode cantilever deflection is detected and measured, in this mode the amplitude of
oscillation typically measured. Positive feedback works in a similar manner to contact mode,
by keeping amplitude constant while scanning.

Pros of intermittent contact mode:

The tip does not scratch the surface, thereby avoiding artifacts. This is extremely
important for soft samples.
The tip typically does not remove parts of the sample.
The Tapping regime allows the collection of various kinds of information related to the
properties of the surface material (phase contrast).

Cons of intermittent contact mode:

Requires extensive operational skill and additional hardware.

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The load force cannot be precisely controlled in particular in liquid environments.

The mode does not allow for fast scanning (typically 0.52 seconds per scan line).

Force Mode
Force mode not an imaging mode .It is used to measure forces acting between AFM tip and
the surface of interest at a specific point. In contrast to the previous modes, the cantilever
does not move in lateral direction. The scanner goes up and down, elevating and approaching
the cantilever to the surface.

Pros of force mode:

Information about surface viscoelastic and elastic properties are provided.

Able to detect long-range forces.
Record the information about tip-surface adhesion force.

Cons of force mode:

Not record the topographical information.

Requires a very clean and homogeneous surface.

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AFM In Study Of Cancer Cells:

Oncogenically transformed cells differ from normal cells in terms of cellcell interaction, cell
growth, morphology, organization of cytoskeleton, and interactions with the extracellular
matrix. Atomic force microscopy is capable of detecting most of these changes. It is
interesting that in the majority of these applications AFM has not been used as just straight
microscopy. In another study, AFM was used as a highly sensitive microscope for early
detection
of
cytotoxic events. In
others, AFM was
used as a highresolution detector
of
erosion
of
collagen substrate
surface caused by
cancer cells.
Apart from these
applications, confocal microscopy (fluorescent optical, in particular) is still superior to AFM for
overall imaging of cells. Using these optical techniques, one can identify many cancer cells by
means of immunofluorescent tags, or just by looking for generally larger than normal nuclei (in
proportion to cell size). Optical imaging is quick and provides robust statistics. The real
advantage of AFM comes from its ability to detect surface interaction, extremely high
sensitivity to any vertical displacements, and capability to measure cell stiffness and
mechanics.

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Figure 1.2. Fluorescent images of human cervical cells:(left) normal and(right) cancer.

The real advantage of AFM comes from its following features:

Ability to detect surface interaction, high sensitivity to any vertical displacements and
capability to measure cell stiffness and mechanics.
Ability to study biological objects.
There are virtually no limitations on the temperature of the solution/sample, chemical
composition, and the type of the medium (can be either non aqueous or aqueous
liquid).
AFM can get information about surfaces in situ and in vitro, in air, in water, buffers, and
other ambient media.
It can scan surfaces with up to nanometer resolution, and up to 0.01 nm vertical
resolution.
True 3D surface topographical information is provided.
It can scan with different forces.

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Transmission Electron Microscopy (TEM)

The transmission electron microscope (TEM), the first type of EM, has many commonalities
with the optical microscope and is a powerful microscope, capable of producing images 1
nanometer in size. They require high voltages to increase the acceleration speed of electrons,
which, once they pass through the sample (transmission), increase the image resolution. The
2-d, black and white images produced by TEMs can be seen on a screen or printed onto a
photographic plate. Although recent innovations in software help to minimize, TEM resolution
is hampered by spherical and chromatic aberrations. The TEM is a popular choice for
nanotechnology as well as semiconductor analysis and production.
A Transmission Electron Microscope (TEM) utilizes energetic electrons
morphologic, compositional and crystallographic information on samples.

to

provide

At a maximum potential magnification of 1 nanometer, TEMs are the most powerful

microscopes. TEMs produce high-resolution, two-dimensional images, allowing for a wide
range of educational, science and industry applications.
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TEMs consist of the following components:

An electron source
Thermionic Gun
Electron beam
Electromagnetic lenses
Vacuum chamber
2 Condensers
Sample stage
Phosphor or fluorescent screen
Computer

Advantages

A Transmission Electron Microscope is an impressive instrument with a number of

advantages such as:

TEMs offer the most powerful magnification, potentially over one million times or
more
TEMs have a wide-range of applications and can be utilized in a variety of different
scientific, educational and industrial fields
TEMs provide information on element and compound structure
Images are high-quality and detailed
TEMs are able to yield information of surface features, shape, size and structure
They are easy to operate with proper training

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Disadvantages
Some cons of electron microscopes include:

TEMs are large and very expensive

Laborious sample preparation
Potential artifacts from sample preparation
Operation and analysis requires special training
Samples are limited to those that are electron transparent, able to tolerate the
vacuum chamber and small enough to fit in the chamber
TEMs require special housing and maintenance
Images are black and white

Characterization of TiO2 nanoparticles.

A representative transmission electron microscopic image of the TiO2 nanoparticles is shown
in Figure 1. The particles had a spherical shape with a diameter of about 25 nm. The particles
had dimensions suitable for escaping rapid renal excretion, as well as avoiding components
of the reticular endothelial system, thus facilitating potentially passive targeting of drugs to
tumors via the enhanced permeation and retention effect and increasing drug accumulation in
tumor cells after endocytosis.

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Figure 1 Transmission electron microscope image of magnetic titanium oxide

nanoparticles.

1.4 Application
Cancer treatment
In mid-1980s Fujishima and co-workers used the strong oxidizing power of illuminated
titanium dioxide to kill tumor cells. In the experiment, polarized illuminated titanium dioxide
film electrodes and colloidal suspensions is used for effective in killing HeLa cells. A series of
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experimental conditions is observed, including the

effect of superoxide dismutase (effect enhancer) due
to the production of peroxide. There is also
possibility in selectively kill a single cancer cell using
a

polarized,

illuminated

titanium

dioxide

microelectrode. Collaborating with few urologists, an

experiment of cancer implanted under animal skin
(mice) to cause tumor to form. About 0.5 cm grew, a
solution containing fine particles of titanium dioxide is injected and after 2 or 3 days irradiated
tumor and repeated it again after 13 days, and observed a marked antineoplastic effect.
Photo excited titanium dioxide particles also suppressed the growth of HeLa cells implanted in
nude mice, compared with those receiving titanium dioxide alone or UV irradiation alone.
However, this technique was not effective in stopping a cancer that had grown beyond a
certain size. The results of animal experiments have shown that near-UV rays, with
wavelengths of 300400 nm, which are used in photo catalytic reactions, are safe and do not
cause mutation to the cell. [2] But this has been improved from recent research, so now,
nanobio technology provide an alternative form of therapy that targets only cancer cell and
does not affect normal living tissue.

Figure 1: Animal test of photocatalytic cancer therapy; photograph of nude mouse just after
initial treatment (A) and 4 weeks after treatment.

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Recent studies:
Scientists from the U.S. Department of Energys (DOE) Argonne National Laboratory and the
University of Chicago Medical Centers Brain Tumor Center achieved a way to specifically
target brain cancer cells. This experiment was using inorganic titanium dioxide which bonded
to antibodies. These composite nanoparticles provide an alternative therapy that target to
cancer cells only. Titanium dioxide also do not affecting nearby normal living tissue.
This new therapy relies on a two-pronged approach. Titanium dioxide is a versatile photo
reactive nanomaterial. It recognize and bind specifically to cancer cells when linked to an
antibody. Focused visible light is shined onto the region, and the localized titanium dioxide
reacts to the light by creating free oxygen radicals that interact with the mitochondria in the
cancer cells. Mitochondria act as cellular energy plants, and it receives a signal to start cell
death when free radicals interfere with their biochemical pathways.

Figure 2: titanium dioxide as targeted drug delivery

Titanium dioxide, is used for targeted drug delivery. Surface is modified with polyethylene
glycol. Folic acid is used as the ligand to target Folate receptor. Paclitaxel is attached to the
surface modified titanium dioxide nanoparticle. A controlled delivery of paclitaxel in vitro is
observed. [4]
X-ray fluorescence microscopy was performed also showed that the tumors invadopodia,
actin-rich micron-scale protrusions that allow the cancer to invade surrounding healthy cells. It
can also be attacked by the titanium dioxide nanoparticles. So far, tests have been done only
on cells in a laboratory setting. Following a 5-minute exposure to focused lights, there was an
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almost 100% cancer cell toxicity rate 6 hours after exposure and 80% toxicity 48 hours after
exposure. The National Cancer Institute supported that a high-performance nanobiophoto
catalyst for targeted brain cancer therapy. [5]

References
[1] Hongbo Shi, Ruth Magaye, Vincent Castranova and Jinshun Zhao, (15 April 2013),
Titanium dioxide nanoparticles: a review of current toxicological data.

[2] Leon Smith, Zdenka Kuncic, Kostya (Ken) Ostrikov, and Shailesh Kumar, (2012),
Nanoparticles
in
Cancer
Imaging
and
Therapy.
Available
from
http://www.hindawi.com/journals/jnm/2012/891318/. Retrieved 14/12/2014.

[3] S.C. Singh, D.P. Singh, J. Singh, P.K. Dubey,R.S. Tiwari and O.N. Srivastava, (No Date),
Metal Oxide Nanostructures; Synthesis, Characterizations and Applications.

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[4] Elsevier B.V, (2013), Folate targeted PEGylated titanium dioxide nanoparticles as a
nanocarrier
for
targeted
paclitaxel
drug
delivery
available
from
http://www.sciencedirect.com/science/article/pii/S0921883113000113. Retrieved14/12/2014.

[5] No name, (September 2009), Titanium Dioxide Nanoparticles Catalyze Brain Tumor
Death.Available from http://nano.cancer.gov/action/news/2009/sep/nanotech_news_2009-0923b.asp. Retrieved 14/12/2014.

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