Using Gold Nanoparticles to Kill Cancer

April 1, 2016
Cancer is an inherently difficult illness to treat.
Sometimes residual cancer cells remain even after
removing tumors; sometimes parts of a tumor
cannot be removed because of the way the cancer
cells attach to a vital organ. A way to detect and
kill cancer cells in vivo has been sought after for a
long time, and some lines of research are finally
showing great promise. The latest? Having cancer
cells envelop dozens of nanoparticles that then are
used to obliterate the cancer cell from the inside,
leaving healthy cells untouched!1

The Gist of It
Essentially, nanoparticle therapy works by getting
about a hundred gold nanoparticles clustered into
a cancer cell, then blasting the area with an
infrared laser pulse. Energy imparted by the laser
causes the fluid around the cluster to reach
temperatures high enough to vaporize the fluid,
which causes a rapid expansion and collapse. This
results in the obliteration of the cancer cell, but
healthy cells are not affected because they don’t
incorporate enough gold particles to cause
damage. As the high temperatures remain
confined within the nanobubble formed around the
cluster, nearby cells are unharmed by the process.
How Do You Get Something Inside a Cell?
Cells can incorporate foreign objects in a number
of ways, but the method that this research utilizes
is called receptor-mediated endocytosis. In this
process, the foreign object attaches itself to a
point on the outside of the cell called a receptor,
which is embedded in the cell’s outer membrane.
Receptors have active ends on either side of the
cell membrane, each of which attaches to certain
molecules; the exterior side is selective for certain
particles that the cell needs, while the interior end
attaches to the proteins and signaling molecules
that regulate cellular processes based on what’s
happening outside the cell. The cell uses this
method, for example, when it ingests a cholesterol
molecule; the molecule binds to a receptor at the
cell membrane, leading proteins to attach to the
interior end of the receptor, thickening the cell
membrane. A pit forms that then envelops the
bound molecules into the cell.

Illustration of receptor–mediated
endocytosis.3 Image Credit: Illustration courtesy of
Professor Emeritus Danton H. O’Day, Department
of Biology, University of Toronto Mississauga,
Canada
Preparing the Nanoparticles
For this therapy to be effective, the gold
nanoparticles have to attach to a cancer cell more
easily than a healthy cell, otherwise the laser pulse
would damage healthy tissue. To accomplish this,
the researchers coated the particles in an antibody
that is known to attach to the specific type of
aggressive cancer they were using in the study,
head and neck squamous cell carcinoma. It is this
antibody that attaches to the receptor at the cell
membrane.
The researchers also found that there was an
optimal size to the gold particles. If the particles
were less then 10 billionths of a meter (10
nanometers) in diameter, the cell would quickly
clear them out. If the particles were greater than
100 nanometers the cell had trouble internalizing
the particles. The scientists found that the
nanoparticles which worked best for their study
were around 60 billionths of a meter in diameter.
These antibody-coated gold nanospheres were
found to insert themselves into cancer cells far
more readily than healthy cells; the average
cluster size in healthy cells was found to be 64
nanometers (about 1 sphere), while the average
cluster size in cancer cells was found to be about
300 nanometers (about 100 spheres).
One natural advantage to this process is that
tumors often have leaky vascular systems, so
when the gold particles are injected intravenously
near the known cancer, they rapidly spread and
are incorporated throughout the cancerous region.
The scientists noted that 24 hours of time was
needed after the injections to allow gold clusters to
form in the cells.
Blowing Up the Cancer Cell
Once the gold nanoparticles are incorporated into
cells, the researchers exposed the tissue to a laser
pulse (near infrared radiation of wavelength 782
nanometers) for a duration of 30 trillionths of a
second (30 picoseconds). This particular type of
laser light is optimal because it penetrates tissue
well and it is not resonant with the gold
nanoparticles. This means that when the light
strikes the nanoparticle it does not absorb it and
immediately start warming the bulk of the gold
nanoparticles resulting in overheating the cell.
Rather, during the first 10 nanoseconds some
melting of the surface without bulk heating of the
gold nanoparticles2 occurs, and this vaporizes the
fluid around the gold nanoparticles. The vaporized
fluid rapidly expands and then collapses. However,
it is imperative to note that the effect is
inconsequential unless there are tens of
nanoparticles in the cluster. The creation of a
nanobubble that rapidly expands and collapses,
with enough energy to destroy a cell, is dependent
on the number of gold spheres in the cluster, with
the severity increasing as the cluster size
increases.
This selectivity of severity with size is what keeps
the healthy cells safe. The gold nanoparticles don’t
do well at transforming the laser pulse to thermal
energy on their own, so any nanobubbles formed
are relatively insignificant—a few spheres together
in a healthy cell will not cause any damage. It is
the cluster of nanoparticles within the cancer cells
that effectively converts the laser pulse to thermal
energy, causing vaporization of the surrounding
fluid, a rapid expansion, and a collapse, leading to
the destruction of the cancer cell. This event is not
easily detected by optical means, but it is easily
“heard” by detecting the sound wave produced
during the rapid expansion and collapse.
Click here to download a video of the process, directly from the
research article!

Taking Out Cancer

This method isn't great at taking out a large
tumor, however the researchers have provided
some evidence of situations where it may be very
useful. If a large number of cancerous cells are
removable, then they should be removed
surgically, but even after removing a bigger tumor,
residual cancer cells can be left behind in the area.
These residual cells can grow into tumors, leaving
the possibility of the cancer recurring. Detecting
single residual cancer cells is not easy, however a
cluster as small as three cancer cells can be
detected using the gold nanoparticle method. This
method then becomes a very useful option for two
reasons: 1) detecting residual cancer cells,
indicating whether more tissue needs to be
removed and 2) using this method to obliterate
residual cancer cells. The researchers had success
with both methods, resulting in no cancer
reappearance in their trials. Removing residual
cancer cells with nanoparticles was deemed a new
type of surgery by the researchers. They called it
“PNB nanosurgery” which stands for Plasmonic
NanoBubble nanosurgery1.

There are some situations, when tumors start to

grow on essential organs, where the tumor is
partially or totally inoperable. In this case, the
nanoparticle method has shown promise in
destroying enough cancer cells to prolong the
patient’s life, albeit not enough to destroy the
abundance of cancer cells.
One of the advantages of PNB surgery is that it
selectively destroys cancer cells, unlike
chemotherapy and radiation therapy. This
improves quality of life and makes surgical
treatment possible for patients ineligible for other
nondiscriminatory treatments1.

Future Research and Development

Future development will be employing PNBs
clinically. According the research article, the
“surgical algorithms for PNB can be integrated into
manual, endoscopic, or robotic surgery by using a
standalone PNB probe or by integrating it with a
surgical endoscope or robotic arm...”1 The
supplementary materials of the research
article1discuss in detail information useful to
applying the technique clinically.
References and Resources
1. Lukianova-Hleb, E., et al., Intraoperative diagnostics and
elimination of residual microtumours with plasmonic
nanobubbles, Nat. Nano 343 (2015)
DOI: 10.1038/NNANO.2015.343
http://www.nature.com/nnano/journal/vaop/ncurrent/full/nnano.
2015.343.html
2. Lukianova-Hleb, E., et al., Transient Enhancement and
Spectral Narrowing of The Photothermal Effect of Plasmonic
Nanoparticles Under Pulsed Excitation, Adv. Mater (25), 772-
776 (2013)
DOI: 10.1002/adma.201204083
http://onlinelibrary.wiley.com/doi/10.1002/adma.201204083/full

3.O’Day, D., Introduction to the Human Cell—The Unit of Life

and Disease, Ebookit, (2012)
https://www.ebookit.com/books/0000001870/Introduction-to-
the-Human-Cell.html?HTSAUsite

4. Service, R., Exploding nanobubbles can kill cancer cells,

Science, 15 Feb 2016
http://www.sciencemag.org/news/2016/02/exploding-
nanobubbles-can-kill-cancer-cells
—H.M. Doss