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Spring Mount Public School: Senior Secondary, CBSE
Spring Mount Public School: Senior Secondary, CBSE
PROJECT REPORT
Submitted in partial fulfilment of the requirement for the award
of
AISSCE
Practical Examination
Submitted by
SAINDAVA VEDHIKA.B.R
Under the guidance of
Mr. K. SARAVANAKUMAR
M.Sc., B.Ed
DEPARTMENT OF CHEMISTRY
MARCH - 2023
CERTIFICATE
This is to certify that the Project entitled “NANO-GOLD FOR CANCER THERAPY”
submitted in partial fulfillment of the requirements for the award of AISSCE practical
examination in CHEMISTRY to SPRING MOUNT PUBLIC, Senior Secondary School,
affiliated to Central Board of Secondary Education, New Delhi, is a record of bonafide work
carried out by SAINDAVA VEDHIKA.B.R ,Reg.No: under my supervision and
guidance, that no part of this project has been submitted for the award of any other
examination and the work has not been published in popular journal or magazine.
I hereby declare that the training entitled “(PROJECT NAME)” submitted to SPRING
MOUNT PUBLIC, Senior Secondary School, affiliated to Central Board of Secondary
Education, New Delhi, in partial fulfillment of the requirements for AISSCE practical
examination is an original work and it has not been previously formed the basis for the award
of any examination during the period of my study.
Date: NAME
Reg No:…………………….
DECLARATION
Apart from the efforts of me, the success of any project depends largely on the
encouragement and guidelines of many others. I take this opportunity to express my gratitude to
the people who have been instrumental in successful completion of this project.
I express my sincere thanks to Dr. NALINI PRBHU SHANKAR BBM., MIB., Correspondent, SPRING
MOUNT PUBLIC SCHOOL for providing me an infrastructure and moral support while carrying out this
project in the school.
I express my deep sense of gratitude to Mrs. MAHALAKSHMI M.Sc., M.Phil., Principal, SPRING
MOUNT PUBLIC SCHOOL who has been continuously motivating and extending their helping hand to us.
I gratefully acknowledge the contribution of the individuals who contributed in bringing this
project up to this level, who continues to look after me despite my flaws.
I express my heartfelt gratitude to my parents for constant encouragement while carrying out this
project.
The guidance and support received from all the members who contributed and who are
contributing to this project, was vital for the success of the project. I am grateful for their constant support
and help.
CONTENT
HISTORY:
Below is a brief history on Nano gold starting from 4th century to Modern era.
1.As a method of staining glass, colloidal gold was used in the 4th century Lycurgus Cup which changes
colour depending on the location of light source.
2. Medieval artisans were the first nanotechnologists. They made stained Glass by mixing Gold chloride into
molten glass. They created tiny gold spheres, which reflected and absorbed sunlight in a way that produced a variety
of colors.
3. Modern scientific Evalution of colloidal gold did not begin until Michael Faraday's work in the 1850s.
1856 is a basement laboratory of Royal Institutions, Faraday accidentally he prepared the first pure sample of
colloidal gold which he called 'activated gold'.
4. In 1898, Theodor Svedberg, who invented ultracentrifugation, and Gustav Mie, who provided the theory
for scattering and absorption by spherical particles, were also interested in the synthesis and properties of colloidal
gold.
THERAPY EXPERIMENTS:
In order to understand how the radiation observing particles of nano gold can help in destroying
tumors we will go through following three experiments.
1. MATERIALS:
Vial of red nano-gold suspension
(Spheres, 12 nm diameter)
Vial of pink nano-gold suspension
(spheres, 80 nm diameter)
Vial of blue nano-gold suspension
(rods, 25 nm axis * 47 nm length)
Vial of water with yellow food coloring
Magnet board.
2. PROCEDURE:
Lay the magnet board flat and set up the four different vials on top.
The substance the solution is composed of are not to be named to the participant and
they should be made at to guess which vial/vials contain Nano-gold particles.
3. OBSERVATIONS:
The participant will likely have guessed the vial with yellow color water to contain the
nano- gold.
4.CONCLUSION:
The vial with yellow food coloring does not contain gold; small difference in the size
can cause the nanoparticles to absorb different wavelengths of light and appear different
colors.
These colors range from red to blue depending on size (red the smallest, blue is largest).
EXPERIMENT ON DETERMINATION OF RIGHT SIZE OF
NANO GOLD:
1. MATERIAL:
2. PROCEDURE:
The participant is to stick out their thumb and hold each flashlight against the tip of the thumb
to see which colored light will pass through.
3. OBSERVATIONS:
3. CONCLUSIONS:
This indicates that red is the right wavelength of light to do cancer therapy as it can pass
through body tissue.
EXPERIMENT TO DETERMINE THE SIZE OF NANO
GOLD TO INJECT IN OUR BODY:
1.MATERIALS:
2. PROCEDURE:
Once again, lay the magnet board flat and set up the three different vials on
top.
The participant must shine the red light through the side of each flask and
note whether the beam of light can pass through the liquid and hit the
magnet board.
3. OBSERVATIONS:
The red light passes through the red and pink solutions.
The red light is absorbed by the blue solutions.
4.CONCLUSIONS:
This indicates that blue nano-gold is the correct particle size to use for
cancer therapy.
TREATMENT:
a) RADIOFREQUENCY THERAPY
X-ray radiography procedures involves the diagnosis of cancer cells through the process of image
acquisition .These techniques rely on the absorption of x-rays on the exposed tissue in order to improve
image quality. In certain radiological procedures such as Radiofrequency therapy, a contrast agent is
injected into the targeted cancer tissue and result in increased x-ray attenuation. Radiofrequency therapy
treatment involves the destruction of tumor cancer tissue cells through the differential heating of cancer
tissue by radio-frequency diathermy. This differential heating is a result of the blood supply in the body
carrying away the heat and cooling the heated tissue. Gold nanoparticles are excellent absorbers of x-rays,
due to its high atomic number of 197Au. This allows for a higher mass of the element, providing for a
greater area of x-ray absorption. By acting as a contrast agent and injected into cancerous tumor cells, it
would result in a higher dose of the cancerous tissue being exposed during radiotherapy
treatment. Additionally gold nanoparticles are more efficiently removed from cells of healthy tissue, in
comparison with cancer cells - a feature that makes them a promising radio sensitizers
ANGIOGENESIS THERAPY:
Angiogenesis is a process involving the formation of new blood vessels from pre-existing vessels. It
involves the degradation of the extracellular matrix, activation, migration, proliferation, and
differentiation of endothelial cells into vessels. It is said to play a large part in the growth and spread of
cancer cells.The process of angiogenesis involves the use of both promoters and inhibitors, balancing the
process by only forming new blood vessels when needed. Examples of promoters include Vascular
Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF) Examples of inhibitors include
Vascular Endothelial Growth Factor Receptor 1, etc.Tumor progression occurs as a result of the transition
from a tumor in the dormant proliferation stage to the active stage as a result of oxygen and nutrients.
This active stage leads to a state of cellular hypoxia, which causes an increased regulation of pro-
angiogenesis proteins such as VEGF. This results in the spreading of inflammatory proteins and cancer
cells alongside the newly created blood vessels.AuNPs have the ability to inhibit angiogenesis by directly
coordinating to heparin binding growth factors. They inhibit phosphorylation of proteins responsible for
angiogenesis in a dose dependent matter. At concentrations 335-670 nM, almost complete inhibition of
phosphorylation was observed. As a consequence of angiogenesis, rheumatoid arthritis has been found to
develop due to the greater ability to spread inflammatory proteins. Through the inhibition of
angiogenesis, the reduction of rheumatoid arthritis is prevalent. In addition, angiogenic inhibitors have a
critical limitation due to the instability of biological conditions and high dosage required. To counter this,
an emerging strategy for the development of therapies targeting tumor-associated angiogenesis through
the use of nanotechnology and anti-angiogenic agents was developed, known as anti-angiogenic therapy.
This approach solved the limitation instability by speeding up the delivery of angiogenesis
inhibitors.Gold nanoparticles display anti-angiogenic properties by inhibiting the function of pro-
angiogenic heparin-binding growth factors (HG – GFs), with prime examples being the vascular
endothelial growth factor 165 (VEGF165) and the basic fibroblast growth factor (bFGF) - both of which
are pro-angiogenic promoters. Studies by Rochelle R. Arvizo, et al. have shown that the use of AuNPs of
various size and surface charge plays an important role in its inhibitory effects.In today’s biological
fields, the use of nanotechnology has allowed for the indirect use of AuNPs to deliver DNA to
mammalian cells; thereby reducing tumor agents and increasing efficiency of electron transfer by
modulating the activity of glucose oxidase. Current ongoing research by the Mayo Clinic laboratories
includes the examination of AuNPs as messengers to deliver reagents capable of manipulating the
angiogenic response in vivo.Current angiogenic inhibitors used today which are approved by
the USFDA to treat cancer is Ayastin, Nexavar, Sutent and Affinitor.
c. HEATING:
Two key factors to consider when irradiating gold nanoparticles in cancer cells are the lattice cooling
rate and lattice heat content. The lattice cooling rate is how fast heat in the particle is distributed to its
surroundings. If the cooling rate for a particle is too low, the lattice heat content can be increased with
moderate energy radiation (40 µJ/fs with 100-fs laser at 800 nm) to the point where gold nanorods can be
melted to create spherical nanoparticles which become photothermally inactive.This decomposition has
been shown using gold nanorods coated with phosphatidylcholine ligands in HeLa cells using a pulsed
laser and were no longer useful for treatment due to their low NIR radiation absorbance. High energy
laser pulses have also been shown to fragment nanorods into smaller particles.While these structural
changes induced by laser pulses could be used to deactivate the photothermal effects of these particles
after treatment, the resulting spherical particles or other particle fragments could lead to complications
during or after treatment when gold nanoparticles are used for clinical treatment and imaging of cancer
cells.A limitation of photothermal chemotherapy using gold nanoparticles involves the choice of laser
when conducting treatment. Pulsed lasers offer very selective treatment of cancer cells within a small,
localized area, but can lead to potential destruction of particles and have a low heating efficiency due to
heat lost during the single pulse excitation. Continuous wave lasers have a higher heating efficiency and
work better in heating larger areas with lower risk of destroying the nanoparticles being heated. However,
treatment with continuous wave lasers are much longer compared to treatment with a pulsed laser.[40] A
limitation of photothermal therapy with respect to the laser used is the depth of the tumor being treated.
Most lasers used to induce tumor ablation using gold nanoparticles can only reach several centimeters
into soft tissue, making it impossible to reach tumors farther in the body. Finding a way to carry out
therapy in cells farther into the body without damaging surrounding cells is essential to making this
technique viable as a cancer treatment in the future.
d. TOXICITY:
After using nanoparticles for photothermal therapy, it has been shown in vitro that high concentrations
of reactive oxygen species (ROS) are formed within the treated cancer cells. While these species are not
of concern to the dead cancer cells, they can cause oxidative stress in surrounding healthy cells if enough
ROS are created leading to healthy cell death. This oxidative stress can be passivated
using polymers as reducing agents (after degradation of the nanoparticle) and damage from ROS can be
reduced using targeted uptake of the nanoparticles to the cancer cells. The mechanism for the oxidative
stress caused by nanoparticles in the body is still the subject of study and provides a possible limitation
when using gold nanoparticles with radiation within the body. While there are many in vitro studies of
gold nanoparticles used for chemotherapy, in vivo studies are both rare and often report conflicting
results. For example, one in vivo study has shown that 13-nm gold nanoparticles circulated in the
bloodstream often “accumulate in the liver and spleen and…have long blood circulation times. Also,
nanoparticles from 8 to 37 nanometers have been shown to cause abnormal symptoms leading to death in
mice due to medical complications in the spleen, liver, and lungs. Yet, other studies have shown that
20 nm gold nanoparticles can pass into the retina without causing any cytotoxic effects and nanoparticles
of 13 nm diameter were not toxic in the body. Many argue that these results differ due to different
concentrations on nanoparticles used for these experiments and requires further research.Biosafety and
biokinetics investigations on biodegradable ultrasmall-in-nano architectures have demonstrated that gold
nanoparticles are able to avoid metal accumulation in organisms through escaping by the renal
pathway.Part of the issue with these studies is the lack of reliable methods for determining the uptake of
gold nanoparticles in vivo without examining the tumor site post-mortem. Gold nanoparticle uptake in
cells is often carried out by examining the organs of injected mice post-mortem. This technique cannot be
replicated during clinical trials, so new methods need to be developed to determine the uptake of cells to
avoid higher concentrations of gold nanoparticles in the body leading to toxic effects. One recently
suggested method to counter this limitation is radiolabeling. The uptake of thiolated gold nanoparticles
has recently been monitored using 111In-labeled polymer shells that surround the gold nanoparticle and
shows a possible way around this problem, but these polymer shells can be removed from the particle
making a more stable labeling system required for these kinds of studies.
d)GOLD NANORODS:
Gold nanorods (GNRs) were first synthesized by , with the first documented use of nanorods for use
in NIR spectrum photothermic therapy being reported in 2006 by . The unique shape of GNRs confers
strong photothermal properties due to the presence of both longitudinal and transverse plasmon. These
strong photothermal properties have been used for anti-tumorigenic applications, many times utilizing
various surface modifications such as conjugating surface antibodies for specific targeting, utilizing
dendrimer stabilization, or even developing a chitosan oligosaccharide surface modification. In one study
performed by Cui et al. GNRs were loaded onto induced pluripotent stem cells (AuNR-iPS) for the
purpose of targeting human gastric cancer cells. It was demonstrated that AuNR-iPS were able to localize
to human gastric cancer tumors and induce thermal-mediated apoptosis and reduction in tumor volume
following NIR irradiation.GNRs appear to be among the most utilized GNP configurations, with
consistent development of GNR based photothermal technologies demonstrated in recent history. In one
such recent study, inorganic phototherapeutic nanocomplexes were created by conjugating GNRs with
defective TiO2 nanoparticle clusters to reduce the need for organic photosensitizers, which are sensitive
to photobleaching and unnecessary energy transfer. These nanoparticle clusters were capable of absorbing
both visible and NIR light from the 500 to 1,000 nm spectrum, demonstrating the ability to induce cell
death in HeLa cells via the photothermal production of ROS. Notable derivatives of GNR configurations
are also coming to the forefront of photothermal cancer therapeutics. In another recent study, the lumens
of halloysite nanotubes (HNTs) were loaded with GNRs and doxorubicin (DOX) following which, the
GNR filled HNTs were conjugated with folic acid using bovine serum albumin for more specific tumor
targeting. By combining the chemotherapeutic approach of DOX with the photothermal capability of
GNRs, it was possible to reduce collateral damage to healthy tissues by DOX while still achieving the
same therapeutic outcomes.
BIBLIOGRAPHY:
1.Seminarsonly.com
2.mrsec.psu.edu
3.Wikipedia