Grayson Winsor

Intro to Nanotechnology

Wesley Sanders

03/21/2018

Gold Nanoparticles and Cancer

Gold Nanoparticles have been a subject of much study in recent years. While they have

been used for since ancient days (such as in the Lycurgus cup, made in the fourth century,) gold

nanoparticles have come under intense scrutiny from medical researchers and scientists alike.

They have been found to have unique properties which allow for better medical treatments for

cancer and tumors. Some of these unique properties include their surface plasmon resonance,

the way they are formed, and capability to be functionalized.

Gold nanoparticles are made using the bottom up approach. The bottom up approach is

taking materials in their basest form and combining them to create something bigger. To make

gold nanoparticles, a water-soluble form of gold is used- HAuCl4, or gold salt. It is then dissolved

in water, producing H+ and AuCl4– ions. The gold ions are floating in the water with one gold

atom per ion. A reducing agent is added, which converts the ions into elemental gold atoms.

These atoms are not soluble in water, so clump together. These clumps are nano-sized, but if

left alone, will continue clumping together, getting bigger and bigger. One way to prevent this is

to put a protective coating on the outer shell of the clumps. This stops more atoms from

attaching to it. If done right, a gold nanoparticle of about 4 nanometers should form (Murphy,

2014).
Gold nanoparticles are also easily functionalized to perform specific duties. Self-Assembled

Monolayers, or SAMs, easily form on noble metal. A noble metal is a metal in which all the

orbitals are full, so can easily interact with many different elements. These self-assembled

monolayers are functionalized with certain materials to perform a certain duty. One of the ways

this enables gold nanoparticles to interact with other molecules. SAMs are made up of three

parts: a sulfur group, or thiols; a carbon chain which connects the other two together; and a

head group, which changes the properties of the film. In the article “Preparation and

Functionalization of Gold Nanoparticles, it states:

It was demonstrated that triphenylphosphine (TPP)-stabilized gold nanoparticles [58]

undergo ligand exchange reactions with a few 􀁚-functionalized thiols to produce

functionalized nanoparticles that preserve the core dimensions of the precursor

particles but exhibit highly increased stability against heat, aggregation, and

decomposition [59]. The strong interaction between n-alkylthiols and the gold surface

provides the most popular method for the attachment of molecular groups (Capek,

2013).

This explains that gold nanoparticles can connect to different molecule groups such as

antibodies that specifically search out cancer cells, allowing researchers to identify their

location and quantity.

Gold nanoparticles have a unique Surface Plasmon Resonance. Surface Plasmon

Resonance (SPR), which is the resonance of electron in the conduction band of a particle. It is

often used as the basis for detecting molecular interactions. In cancer research, gold

nanoparticles are used as a vehicle to deliver biomolecules. They can be functionalized with
plasmid DNA to seek out cancerous cells. Researchers can then search for their specific SPR to

locate those cancerous cells and deal with them before they become dangerous. Gold

nanoparticle’s SPR band is about 520 nm. Also, gold nanoparticles have a distinct Local Surface

Plasmon Resonance (LSPR), which has a greater special resolution than normal SPR, granting

greater accuracy during analysis. SPR along with LSPR allow scientists to locate problem cells

with greater accuracy to them analyze them to determine what the following steps will be in

treatment (Nicoya Lifesciences).

Treatments

Cytotoxicity

One of the treatments that is currently being used for cancer is using cytotoxicity.

Cytotoxicity is when a cell kills itself. The reason that cancer is so dangerous is because there is

unregulated cell growth. In the lifetime of a cell, it goes through different phases. One of these

phases is reproduction. After reproduction, there is a “checkpoint” where enzymes tell the cell

to continue reproducing or to stop. Cancer happens when this “checkpoint” is broken and

doesn’t tell the cell to stop reproducing. This uncontrollable reproduction mass produces cells

that are unable to stop and get rid of themselves through cytotoxicity, causing potential harm

to the body. Scientists have searched for ways to treat this broken “checkpoint”. They have

found that gold nanoparticles (referred to as Au[III] in the article) have the ability to induce

cytotoxicity and inhibit the growth and reproduction of cells.

The accumulated data suggested that MZ molecules were coordinated to the metal ions

by its imine nitrogen as a monodentate ligand and the structures of complexes were six-

coordinate for Fe(III) and four coordinate for the other metal ions. Cytotoxicity assays
 for Au(III) complex were conducted using two human cancer cell lines. The complex

demonstrated significant inhibitory effect on the cell growth of HepG2 with an IC50

value of 1.12±0.2 μM. Therefore, it can be proposed as the potential hemotherapeutic

agent for human hepatocellular carcinoma. (Adam, 2016)

This discovery will help control cancer cells before they spread out of control and become

dangerous by inhibiting them from growing even more and inducing them to kill themselves

before they become dangerous.

Photothermal Therapy

A man named John Kanzius came up with a new way to treat cancer. He took gold

nanoparticles and injected them into the cancerous areas. He then fired radio waves through

those areas, heating up the nanoparticles and killing the cancer cells. He died before being able

to complete his work, but many scientists have built on his idea (Gannon, 2007).

Gold nanoparticles can be functionalized for a purpose. In the case of cancer, scientists

functionalize these nanoparticles with cancer seeking antibodies. When they arrive, the cancer

cells take them into themselves, which amplifies their light absorption. The gold nanoparticles

are Near Infrared (NIR) invisible until they clump up inside the cell, which reduces heating in the

blood and other non-target cells, protecting them from damage (Hainfeld, 2014)

Gold nanoparticles can absorb certain frequencies of light based on their size. For

example, a 40 nm particle can absorb a maximum wavelength of 530 nm of light (Hainfeld,

2014). Light is not readily absorbed into skin tissue at those wavelengths, so clinically that size

of nanoparticle would not be recommended. The optimal wavelength of light for tissue

penetration is around 800 nm NIR. This is because “hemoglobin absorption is decreasing and
water absorption is increasing, forming a ‘‘tissue window’’ of best transmission” (Hainfeld,

2014). This allows the waves to pass through the skin and other tissue to strike the

nanoparticles inside the cancer cells.

Gold nanorods were also found to be effective for treatment. They are about 50-100 nm

in length and absorb NIR wavelengths in their axial direction. “90 nm rods are more

efficient by a factor of 10 than 140 nm nano-shells, based on a per volume basis because

nanorods, unlike nano-shells, contain no large silica particles” (Hainfeld, 2014), allowing for

more absorption.

When the nanoparticles are inside the tumor cells, their phototonic absorption is

amplified by being catalytically aggregated to the cell. This is done using various enzymes and

pH effects by the cells themselves. This increased absorption causes the nanoparticles to

receive a higher energy from lasers, heating them up and killing the cells they are within.

Because of the NIR wavelength, no other cells are damaged in the process (Hainfeld, 2014)

Using gold nanoparticles as part of a treatment for cancer has quickly become a highly

researched area. Gold nanoparticles themselves display unique properties which allow them to

interact with other molecules and cells in a distinct way, such as being functionalized with

antibodies to seek out cancer cells and attach to them. They also have a distinct Surface

Plasmon Resonance which allows scientists to locate them inside tumor cells, more accurately

giving specific locations and detail of the cancer. They can absorb wavelengths of light, heating

up and killing the target cells, leaving non-target cells alone. It is a safe way to conduct

chemotherapy, protecting the patient and their health.

 Works Cited

Adam A. Synthesis, characterization, and cytotoxic in vitro studies of the antibiotic drug

metronidazole complexed with Au(III), Fe(III), Pd(III), and Zn(II): Toward potent gold-drug

nanoparticles in cancer chemotherapy. Russian Journal of General Chemistry [serial online].

2016, 86, 1137-1143.

Capek, Ignac. Preparation and Functionalization of Gold Nanoparticles. J. Surface Sci. Technol.

[serial online] 2013, 29, 1-18

Gannon, Christopher J., et al. “Carbon Nanotube-Enhanced Thermal Destruction of Cancer Cells

in a noninvasive Radiofrequency Field.” Cancer, Wiley-Blackwell, 24 Oct. 2007,

onlinelibrary.wiley.com/doi/full/10.1002/cncr23155.

Hainfeld J, O’Connor M, Lin P, Qian L, Slatkin D, Smilowitz H. Infrared-Transparent Gold

Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by

Photothermal Therapy. Plos One [serial online]. 2014, 9, 1-11.

Murphy, Cathy. “Two Ways to Make Nanoparticles.” Sustainable Nano, Center for Sustainable

Nanotechnology, 10 June 2014, sustainale-nano.com/2014/06/10/two-ways-to-make-

nanoparticles/.
“Localized Surface Plasmon Resonance Theroy.” Nicoya Lifesciences – Revolutionizing Surface

Plasmon Resonance, nicoyalife.com/technology/surface-plasmon-resonance/localized-surface-

plasmon-resonance-theory/