UNIVERSITY OF SCIENCE AND TECHNOLOGY OF HANOI

=====o0o=====

Course: Biomedical Nanotechnology

Lecturer: Pham Van Nhat

FINAL REPORT

TOPIC: GOLD NANOPARTICLES (AuNPS) FOR

CANCER RADIOTHERAPY AND DIANOSIS

Student: Pham Gia Nguyen BA12-142

Page 1 of 9
Abstract
Finding new and better cancer therapies is a big global issue, as cancer is still a deadly illness.
Because of the distinctive qualities and adaptability, gold nanoparticles (AuNPs) are among the most
researched nanomaterials for biological applications, particularly in the field of cancer research from
early detection to diagnosis and treatment, including radiotherapy. Thus, this report aimed to highlight
some basic knowledge of AuNPs and all their functions in cancer radiotherapy as radiosensitizers.

Introduction
According to WHO statistics, there are nearly 10 million deaths around the world in 2022 that
were related to cancer. This led cancer to the most significant reason. Nowadays, the primary
treatments for cancer include radiation, chemotherapy or also surgery, which can be done individually
or combined variously. For about half of all cancer patients, radiation therapy is a critical and effective
form of treatment. This therapy aims to damage the cancer cells in the tumor or their blood vessels to a
degree that either kills the tumor or starves it. This is typically achieved by irradiating the tumor cells
with high-energy Gamma rays, X-rays (photons), or intense ion beams

To enhance the effectiveness of radiotherapy, many innovative techniques have recently been
developed, incorporating gold nanoparticles (AuNPs) and their impact on tumor cells. Gold
nanoparticles are potent radiosensitizers in cancer therapy, offering multiple functions from diagnosis
to treatment. This report aims to provide a concise overview and explanation of gold nanoparticles,
outline various synthesis methods to create AuNPs, and explore different applications and advantages
of these nanoparticles in cancer radiotherapy

Overview of Gold nanoparticles (AuNPs)

Gold (Z=79) has long been recognized as a rare and durable metal, known for its ease of
handling, construction, and involvement in various chemical reactions. In its pure form, gold appears as
a bright yellow, soft, and malleable solid under standard conditions. The medical applications of gold
and its complexes have a rich history, running parallel to its practical use value.

Page 2 of 9
 Today, noble metal nanoparticles are gaining significant attention. Gold nanoparticles (AuNPs),
in particular, are at the forefront of scientific research due to their numerous properties and potential
applications in clinical chemistry, bioimaging, cancer therapy, and targeted drug delivery. AuNPs are
especially notable for their exceptional and possibly unique physical, chemical, optical, and electronic
properties, which render them ideal for developing highly multifunctional platforms for biochemical
applications. As a result, AuNPs are among the most studied and highly promising nanomaterials.

Figure 1:The adaptability of AuNPs in synthesis. Fine-tuning of particle attributes is made possible by AuNPs, which provide a special platform for
simple modification of particle size, shape, surface coating, and functionalization [7].

The shape of nanoparticles can be demonstrated into some shapes, including hollow
nanospheres, nanorods, nano-shells, nanocages and nano-stars (Figure 1). Nanoparticle’s shape can
affect how long it stays in the bloodstream and accumulates at a certain location such as in tumor cells,
for instance, non-spherical particles circulating for a longer period.

Surface properties
One of the key characteristics of gold nanoparticles that might affect how the particles and cells
interact is their surface. The pathways for internalization and the way a nanoparticle interacts with a
cell are dictated by its surface charge, neutral and anionic-charged particles have better cell
Page 3 of 9
permeability. Additionally, to escape macrophage capture, the surface of nanoparticles (NPs) should be
hydrophilic. The fundamental process is endocytosis, which entails the absorption of NPs in membrane
invasions, the formation of endocytic vesicles, and subsequent transport of these vesicles to certain
intracellular compartments. Additionally, with changing the protective coating surrounding, NPs may
be altered to regulate their solubility, stability, and interactions with the biological environment. Based
on their surface charge, nanoparticles can influence their entry into cells and interact with them;
particles with neutral and negative charges have better permeabilities. The fundamental process is
endocytosis, which entails absorbing nanoparticles into clefts in the cell membrane, creating endocytic
vesicles, and distributing them to certain regions of the cell.

There are many materials that can be as capping agents for the polymer coat of AuNPs to play a
role in protecting them from opsonization. Based on the development in surface coating technology, the
possibility of surface functionalization of AuNPs has been improved (Figure 1). Hydrophilic polymers
or surfactants on the surface of nanoparticles enhance their circulation throughout the circulatory
system. Other polymers, plasma proteins, or opsonin are unable to interact with hydrophilic polymer
chains linked on the surface of the nanoparticles. Hydrophilic polymers function as a bridge between
corrosive cells and nanoparticles, shielding them from opsonization and immune system recognition.
Due to this, AuNPs has been used widely in biomedical applications, including imaging (CT,
photoacoustic imaging, surface enhance Raman scattering), delivery drugs, biosensors and therapy
(radiotherapy as radiosensitizers, photothermal therapy)

General synthesis of Gold Nanoparticles (AuNPs)

Gold nanoparticles can be synthesized by using two approaches such as the “bottom-up” and the
“top-down” approach. In general, there are two categories into which the techniques may be placed: the
first is based on the synthesis method, and the second is based on the methodological approach. AuNPs
may be produced with specific sizes and forms by combining with regulated synthesis techniques

Page 4 of 9
 Figure 2:TEM and SEM micrographs of gold nanoparticles

The most common and simple method for synthesis AuNPs is the Turkevich method (1951),
which results in AuNPs measuring about 20 nm in diameter. Then, in 1973, it was modified by Frens.
This technique based on the reduction of chloroauric acid (HauCl 4 ) by citrate in boiling water.
Depending on the initial sodium citrate level, aqueous solutions of fairly monodisperse spherical
nanoparticles with diameters ranging from 15 to 150 nm might be obtained from this reaction.

Figure 3: Synthesis AuNPs by using Turkeyvich method

Mechanisms of AuNPs for Cancer Radiotherapy

In cancer radiotherapy, gold nanoparticles (AuNPs) serve as effective radiosensitizers. Initially,
the theory behind AuNP radiosensitization was thought to solely involve physical dose enhancement
due to gold's high photoelectric absorption. However, recent experimental data indicate that biological
and chemical contributions are also significant, suggesting that AuNPs are involved in all three stages
Page 5 of 9
of interaction with ionizing radiation (IR). While the exact mechanisms driving AuNP-induced dosage
augmentation remain unclear, these processes are explained in relation to the three stages of radiation
exposure affecting biological systems.
1. Physical Enhancement
Energy Absorption: AuNPs have different energy-absorbing properties compared to soft
tissues, enabling physical dose enhancement. Low energy electrons are crucial for the dose
augmentation provided by AuNPs, with the energy released being nanoscale in nature. Studies
have shown that low energy photons can make cells radiosensitive in vitro, whereas higher
energy photons fail to produce dose enhancement. These low energy electrons are mainly
responsible for DNA damage, highlighting the importance of short-range electrons.
Photon Interaction: At kilovolt energies, photons interact with matter primarily through
the Compton effect or the photoelectric effect. Both processes result in the ejection of electrons
and the release of lower energy photons and secondary electrons.
Atomic Number Dependency: AuNPs can provide more energy per unit mass by
leveraging the atomic number difference between soft tissues and gold. This increases the local
radiation dose deposited at the target tumor, as the X-ray cross section, dependent on the atomic
number of the interacting atom, represents the likelihood of material interacting with radiation.
2. Chemical Enhancement
Free Radical Processes: AuNPs participate in free radical processes that help overcome
damage or degrade DNA links, making DNA more susceptible to radiation damage. Chemical
enhancement mechanisms can occur based on the cellular location of AuNPs: chemical
enhancement of DNA and enhanced free radical formation and catalysis. In the nucleus, AuNPs
can bind to DNA, leading to radiation enhancement. They can also interact with hydrogen
peroxide (H2O2) or superoxide anions (O2−) to transform organic compounds through catalytic
processes. Studies have shown that AuNPs interact with molecular oxygen on their surface to
promote surface-mediated electron transfer, catalyzing the creation of Reactive Oxygen Species
(ROS).
3. Biological Enhancement
Radiosensitization Mechanisms: AuNPs make cells more susceptible to the redox-active
substance bleomycin. DNA damage and oxidative stress can be used to destroy cells,
demonstrating biological enhancement. The three main mechanisms of radiosensitization are
ROS production, oxidative stress and mitochondrial dysfunction, cell cycle disruption,
and DNA repair inhibition. o ROS Production, Oxidative Stress, and Mitochondrial
Dysfunction: The interaction of free radicals and ROS generated by water radiolysis with
various cellular macromolecules results in apoptosis or cell death. AuNPs of different sizes,
shapes, and surface functions can efficiently trigger ROS creation. Superoxide anion radicals
(O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH) can directly or indirectly harm
cells by interacting with biomolecules or by oxidizing lipids, proteins, and DNA, as well as
disrupting mitochondria.
Cell Cycle Disruption: The cell cycle affects the sensitivity of cells to ionizing radiation.
Cells display varying degrees of radiosensitivity at different stages of the cell cycle; the most

Page 6 of 9
 radioresistant cells are in the late S phase, while the most sensitive cells are in the G2/M phase.
AuNPs can increase radiation sensitivity by altering cell cycle distribution and increasing the
concentration of G2/M phase cells.
DNA Repair Inhibition: Radiation treatment can cause various types of DNA damage,
including single-strand breaks (SSBs), double-strand breaks (DSBs), DNA-protein cross-links,
and changes to DNA bases. Another important biological mechanism of AuNP radiosensitization
is DNA repair inhibition. AuNPs can affect the speed of DNA repair when exposed to radiation.
The presence of AuNPs can alter the dynamics of γ-H2AX and 53BP1 foci formation and
disappearance, potentially indicating a slower rate of DNA repair. The interaction between
AuNPs and γ-H2AX and 53BP1 foci could lead to radio sensitization, enhancing the
effectiveness of radiation therapy.

Application of Gold Nanoparticles (AuNPs) in Cancer

Diagnosis
Gold nanoparticles (GNPs) have emerged as versatile tools in various imaging modalities for the
detection and monitoring of gastrointestinal cancer. Their application spans across techniques such as
CT imaging, magnetic resonance imaging (MRI), and photoacoustic imaging. GNPs surpass traditional
iodine contrast agents in CT imaging due to their high X-ray absorption coefficient and
biocompatibility, and they can be customized with antibodies and ligands to target specific cancer cells
and biomarkers, enhancing CT scan contrast. For instance, HSP70 antibody-conjugated GNPs exhibit
exceptional sensitivity and specificity in targeting colon cancer cells. In MRI, GNPs serve as T2
contrast agents when combined with magnetic materials like iron oxide, which enhances the stability
and circulation time of probes, enabling dual-mode imaging with planar and photoacoustic signals.
Additionally, iron oxide-coated GNPs can target gastric cancer cells, providing both red fluorescence
and T2 contrast. In photoacoustic imaging, GNPs generate robust signals in the near-infrared region
through the surface plasmon resonance effect, allowing for deep tissue penetration and high-resolution
imaging. Beyond imaging, GNPs facilitate the delivery of drugs or genes to tumor sites, enabling the
monitoring of distribution and efficacy. For example, miR-26a-loaded GNPs modified with hyaluronic
acid effectively target and prevent hepatocellular carcinoma, offering insights through photoacoustic
imaging. Moreover, GNPs are utilized in optical coherence tomography, terahertz imaging, and
fluorescence imaging, leveraging their unique properties and surface activity. By enhancing sensitivity
and specificity, GNPs enable multi-modal imaging using various techniques. A noteworthy example
involves GNPs synthesized by tumor cells, released from twosomes, and employed for imaging, CT,
and MRI of hepatocellular carcinoma. In summary, GNPs have proven to be promising tools in the
realm of gastrointestinal cancer imaging, showcasing their adaptability and effectiveness across diverse
imaging modalities.

Discussion
Gold nanoparticles (AuNPs) possess numerous attractive properties that make them valuable for
cancer treatment. Due to the Enhanced Permeability and Retention (EPR) effect, they are small and

Page 7 of 9
distribute broadly throughout the body, preferentially accumulating at tumor sites. AuNPs can bind
with various proteins and medications, enabling them to actively target cancer cells that overexpress
cell surface receptors. Although AuNPs are biocompatible, certain preparations can be hazardous in
both in vitro and in vivo settings.
AuNPs have a high atomic number, resulting in greater X-ray absorption and providing higher
contrast compared to standard agents. Additionally, at kilovoltage energies, AuNPs have been
demonstrated to induce radiosensitization. When exposed to specific types of light, AuNPs resonate
and generate heat, which can be employed in tumor-selective photothermal treatment. Despite their
great promise, several challenges must be addressed before AuNPs can be routinely deployed in
clinical settings. These challenges include toxicity, the effects of various factors, and circulation time.

Conclusion
This report has provided an overview of the basic knowledge of AuNPs, their advantages, and
their roles in cancer therapy, specifically as radiosensitizers in radiotherapy and diagnosis. The
mechanisms by which gold nanoparticles enhance cancer treatment through radiation have also been
demonstrated in this report.

References
1. S. Medici, M. Peana, D. Coradduzza, and M. A. Zoroddu, “Gold nanoparticles and cancer:
Detection, diagnosis and therapy,” Seminars in Cancer Biology, vol. 76, pp. 27–37, Nov. 2021,
doi: 10.1016/j.semcancer.2021.06.017.
2. A. J. Mieszawska, W. J. M. Mulder, Z. A. Fayad, and D. P. Cormode, “Multifunctional Gold
Nanoparticles for Diagnosis and Therapy of Disease,” Mol. Pharmaceutics, vol. 10, no. 3, pp.
831–847, Mar. 2013, doi: 10.1021/mp3005885.
3. Y.-C. Yeh, B. Creran, and V. M. Rotello, “Gold nanoparticles: preparation, properties, and
applications in bionanotechnology,” Nanoscale, vol. 4, no. 6, pp. 1871–1880, 2012, doi:
10.1039/C1NR11188D.
4. K. Mahato et al., “Gold nanoparticle surface engineering strategies and their applications in
biomedicine and diagnostics,” 3 Biotech, vol. 9, no. 2, p. 57, Feb. 2019, doi: 10.1007/s13205-
019-1577-z.
5. J. Pérez-Juste, I. Pastoriza-Santos, L. M. Liz-Marzán, and P. Mulvaney, “Gold nanorods:
Synthesis, characterization and applications,” Coordination Chemistry Reviews, vol. 249, no.
17–18, pp. 1870–1901, Sep. 2005, doi: 10.1016/j.ccr.2005.01.030.
6. B. Janic et al., “Therapeutic enhancement of radiation and immunomodulation by gold
nanoparticles in triple negative breast cancer,” Cancer Biol Ther, vol. 22, no. 2, pp. 124–135,
Feb. 2021, doi: 10.1080/15384047.2020.1861923.8

Page 8 of 9
7. S. Her, D. A. Jaffray, and C. Allen, “Gold nanoparticles for applications in cancer radiotherapy:
Mechanisms and recent advancements,” Advanced Drug Delivery Reviews, vol. 109, pp. 84–
101, Jan. 2017, doi: 10.1016/j.addr.2015.12.012.
8. X. Huang et al., “Astatine-211-Labeled Gold Nanoparticles for Targeted Alpha-Particle Therapy
via Intravenous Injection,” Pharmaceutics, vol. 14, no. 12, p. 2705, Dec. 2022, doi:
10.3390/pharmaceutics14122705.
9. P. Ghosh, G. Han, M. De, C. Kim, and V. Rotello, “Gold nanoparticles in delivery
applications☆,” Advanced Drug Delivery Reviews, vol. 60, no. 11, pp. 1307–1315, Aug. 2008,
doi: 10.1016/j.addr.2008.03.016.
10. K. Saha, S. S. Agasti, C. Kim, X. Li, and V. M. Rotello, “Gold Nanoparticles in Chemical and
Biological Sensing,” Chem. Rev., vol. 112, no. 5, pp. 2739–2779, May 2012, doi:
10.1021/cr2001178.
11. P. Huang et al., “Folic acid-conjugated Silica-modified gold nanorods for X-ray/CT imaging-
guided dual-mode radiation and photo-thermal therapy,” Biomaterials, vol. 32, no. 36, pp. 9796–
9809, Dec. 2011, doi: 10.1016/j.biomaterials.2011.08.086.
12. Y. Chen, J. Yang, S. Fu, and J. Wu, “Gold Nanoparticles as Radiosensitizers in Cancer
Radiotherapy,” Int J Nanomedicine, vol. 15, pp. 9407–9430, 2020, doi: 10.2147/IJN.S272902.
13. S. Jain, D. G. Hirst, and J. M. O’Sullivan, “Gold nanoparticles as novel agents for cancer
therapy,” Br J Radiol, vol. 85, no. 1010, pp. 101–113, Feb. 2012, doi: 10.1259/bjr/59448833.
14. P. Deveci, “Synthesis, optical properties and photherapy applications of gold nanostars,” J Incl
Phenom Macrocycl Chem, vol. 99, no. 1–2, pp. 23–31, Feb. 2021, doi: 10.1007/s10847-020-
01035-5.
15. M. Yafout, A. Ousaid, Y. Khayati, and I. S. El Otmani, “Gold nanoparticles as a drug delivery
system for standard chemotherapeutics: A new lead for targeted pharmacological cancer
treatments,” Scientific African, vol. 11, p. e00685, Mar. 2021, doi: 10.1016/j.sciaf.2020.e00685.

Page 9 of 9