This false color image shows the embedding of hollow gold particles inside silicon wafers. The gold particles heat up quickly when harmless infrared radiation is shone upon them, causing nearby tissue (in this case, breast cancer cells) to die. |
By
shining infrared light on specially designed, gold-filled silicon
wafers, scientists at The Methodist Hospital Research Institute have
successfully targeted and burned breast cancer cells. If the technology
is shown to work in human clinical trials, it could provide patients a
non-invasive alternative to surgical ablation, and could be used in
conjunction with traditional cancer treatments, such as chemotherapy, to
make those treatments more effective.
The research is presented in the first issue of the new Advanced Healthcare Materials, a Wiley journal.
“Hollow
gold nanoparticles can generate heat if they are hit with a
near-infrared laser,” said Research Institute Assistant Member Haifa
Shen, M.D., Ph.D., the report’s lead author. “Multiple investigators
have tried to use gold nanoparticles for cancer treatment, but the
efficiency has not been very good—they’d need a lot of gold
nanoparticles to treat a tumor.”
Instead,
Shen and his colleagues turned to a technology developed by the study’s
principal investigator, Mauro Ferrari, Ph.D., The Methodist Hospital
Research Institute (TMHRI) president and CEO, to amplify the gold
particles’ response to infrared light.
“We
developed a system based on Dr. Ferrari’s multi-stage vector technology
platform to treat cancers with heat,” Shen said. “We found that heat
generation was much more efficient when we loaded gold nanoparticles
into porous silicon, the carrier of the multistage vectors.”
Shen
and his team found that in the presence of 808-nm light, the
gold-filled silicon particles heated up a surrounding solution by about
20 C (35 F) in seven minutes. Water particles immediately around the
particles were presumed to have been hotter.
And
experiments showed that tumor cell growth was lowest in the presence of
gold-loaded silicon nanoparticles in three types of breast cancer
cells—MDA-MB-231 and SK-BR-3 (human), and 4T1 (mouse).
The
silicon wafers the scientists are using are the result of painstaking
work by Ferrari’s group to design nanoparticles that preferentially bind
to breast cancer cells, rather than, say, healthy liver or immune
system cells. The shape and size of the silicon particles, as well as
their surface chemistry, are all crucial, Ferrari’s group found. Too big
or the wrong shape, and the silicon nanoparticles bind to multiple cell
types—or none at all. Polyamine structures are attached to the wafers
to improve their attraction to cancer cell surfaces and their
solubility. The wafers are about one micrometer in diameter
(one-thousandth of a millimeter). By contrast, the typical breast cancer
cell is about 10 to 12 times that size.
Shen says the gold particles, too, must be designed with a specific use in mind, albeit for indirect reasons.
“The
hollow gold particles we load into the porous silicon must be the right
size and have the correct-sized space inside them to interact with the
infrared light we are using,” he said. “But the wavelength of infrared
we use will have to change depending on where the tumor is. If it’s
close to the skin, we can use shorter wavelengths. Deeper inside the
body, we have to use longer wavelengths of infrared to penetrate the
tissue. The hollow space of the gold particles must be modified in
response to that.”
Both
silicon and gold have low toxicity profiles in the human body, and are
popular materials in current investigations using medical
nanotechnology. Silicon is steadily broken down by physiological
processes into an acid that is removed through the kidneys. And gold is
chemically inert.
And
infrared—the type of light used by TV remote controls and garage door
openers—is also far less dangerous than light with shorter wavelengths,
such as ultraviolet, which can cause DNA damage, and X-rays.
Understanding
why hollow gold particles heat up in the presence of certain
wavelengths of infrared is complex enough to require some background in
physical chemistry. But the upshot is that the energy of certain
wavelengths of light is largely absorbed by the particles, and that
energy is released as vibrational (heat) energy. Absorption is
influenced both by the diameter of the space within the hollow gold
particles, and by the properties of gold itself.
Shen
says he’d like to know whether the silicon-gold nanotechnology can be
used to wipe out whole tumors, rather than just cancerous cells.
“We
are planning pre-clinical studies to study the technology’s impact on
whole tissues, breast cancer cells and possibly pancreatic cancer
cells,” Shen said. “We would also like to see whether this approach
makes chemotherapy more effective, meaning you could use less drugs to
achieve the same degree of success in treating tumors. These
investigations are next.”
Coauthors of the Advanced Healthcare Materials paper were Jian You, whose contributions were equal to Shen’s, Guodong Zhang, Arturas Ziemys,
Qingpo Li, Litao Bai, Xiaoyong Deng, Donald R. Erm, Xuewu Liu, Chun Li,
and Mauro Ferrari. The research was supported with grants to Ferrari
from the Department of Defense and the National Institutes of Health.
Cooperative, Nanoparticle-Enabled Thermal Therapy of Breast Cancer