March 27, 2006
New Shapes of Nano Gold Yield Improved Properties for
Cancer Imaging and Therapy
Researchers at the Georgia Institute of Technology and the University of California, San Francisco (UCSF), who had previously shown that gold nanoparticles have potential in noninvasive cancer treatment and imaging (click here for earlier stories), have found an even more effective and safer way to detect and kill cancer cells. By changing the shapes of gold nanospheres into cylindrical gold nanorods, they can detect malignant tumors hidden deeper under the skin, as is the case with breast cancer, and selectively destroy them with lasers only half as powerful as before — without harming the healthy cells. The method, which allows for a safer, deeper penetrating noninvasive cancer treatment, has been published in the Journal of the American Chemical Society.
Last year, the father-and-son research team of Mostafa El-Sayed, Ph.D., of Georgia Tech, and Ivan El-Sayed, M.D., of UCSF, showed that gold nanoparticles coated with a cancer antibody were very effective at binding to tumor cells. When bound to the gold, the cancer cells scattered light, making it very easy to identify the noncancerous cells from the malignant ones. The nanoparticles also absorbed the laser light more easily, so that the coated malignant cells only required half the laser energy to be killed compared to the benign cells. This makes it relatively easy to ensure that only the malignant cells are being destroyed.
Now, they've discovered that by changing the spheres into rods, they can lower the frequency to which the nanoparticles respond from the visible light spectrum used by the nanospheres to the near-infrared spectrum. Since near-infrared lasers can penetrate deeper under the skin than lasers in the visible spectrum, they can reach tumors that are inaccessible to visible lasers.
"With the nanospheres we're using visible lasers, but most of the solid cancer is under the tissues and visible light doesn't go but a few millimeters deep. But by using the nanorods we can tune them to react to the infrared lasers, which can penetrate the tumor without being absorbed by the tissues," said Mostafa El-Sayed.
Many cancer cells have a protein, known as Epidermal Growth Factor Receptor (EGFR), all over their surface, while healthy cells typically express far less of this protein. By conjugating, or binding, the gold nanorods to an antibody for EGFR, suitably named anti-EGFR, researchers were able to get the nanoparticles to attach themselves to the cancer cells.
In this latest study, researchers incubated two malignant oral epithelial cell lines and one benign epithelial cell line with nanorods conjugated to anti-EGFR. Not only were the malignant lines clearly identifiable as such under a simple optical microscope, but after being exposed to a continuous sapphire laser in the near infrared spectrum, the malignant lines only required half the laser energy to kill them as did the healthy cells.
"This makes it more practical than the sphere in terms of treating cancer," said Mostafa El-Sayed. "For laser phototherapy treatment of skin cancer or for diagnostic biopsies, the spheres are fine, but for phototherapy of cancer deep under the skin, like breast cancer, then one really needs to use the nanorods treatment."
In the meantime, a team of investigators at Rice University have also found that elongated nanostructures have a unique set of optical properties that could be useful in various cancer research applications. This group of researchers, headed by Naomi Halas, Ph.D., has developed gold “nanorice," a layered structure of gold and iron that looks like a nanoscale piece of rice. This work has appeared in the journal Nano Letters.
"On the nanoscale, the shape of a particle plays a critical role in how it interacts with light," said Halas. "We were looking for a new shape that would combine the best properties of the two most optically useful shapes — spheres and rods. It's just a coincidence that that shape turned out to look exactly like a grain of rice."
Nanoparticles like nanorice can be used to focus light on small regions of space. Rice's scientists plan to capitalize on this by attaching grains of nanorice to scanning probe microscopes. By moving the grains next to proteins and unmapped features on the surfaces of cells, they hope to get a far clearer picture than what's available with current technology.
In form, nanorice is similar to nanoshells, a spherical nanoparticle Halas invented in 1998 that is currently being examined for possible applications in molecular imaging, cancer treatment, medical diagnostics and chemical sensing. Both nanorice and nanoshells are made of a non-conducting core that is covered by a metallic shell. But the Rice team’s investigations found that nanorice possesses far greater structural tunability than nanoshells and another commonly studied optical nanoparticle, the nanorod. In fact, tests indicate that nanorice is the most sensitive surface plasmon resonance (SPR) nanosensor yet devised.
Research over the past decade has shown that nanoscale objects can amplify and focus light in ways scientists never imagined. The "how" of this involves plasmons, ripples of waves in the ocean of electrons that flow constantly across the surfaces of metals. When light of a specific frequency strikes a plasmon that oscillates at a compatible frequency, the energy from the light is converted into electrical energy that propagates, as plasmons, through the nanostructure.
Changing the shape of a metal at the nanoscale allows engineers and scientists to modify the properties of these plasmon waves, controlling the way that the metal nanostructure responds to light. Because of this, metal nanostructures can have beautiful, vivid colors that depend on their shape. Some nanoscale structures — like nanorice and nanoshells — act as superlenses that can amplify light waves and focus them to spot sizes far smaller than a wavelength of light. This could allow the detection and characterization of individual biomolecules involved in the cancer process.
Last year, for example, Halas and colleagues showed that nanoshells were about 10,000 times more effective at Surface-enhanced Raman Scattering (SERS) than traditional methods. Raman Scattering is a type of spectrographic technique used by medical researchers, drug designers, chemists and others to determine the precise chemical makeup of materials.
The work with gold nanorods was detailed in a paper titled, “Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods.” This paper was published online in advance of print publication. An abstract is available at the journal’s website.
The work with gold nanorice is detailed in a paper titled, “Nanorice: a hybrid plasmonic nanostructure.” This paper was published online in advance of print publication. An abstract is available at the journal’s website.
Image of a cancer cell illuminated by gold nanorods bound to anti-EGFR. Image courtesy of Mostafa El-Sayed, Georgia Tech.
Nanorice is made of non-conducting iron oxide called hematite that's covered with gold. The core size and shell thickness vary slightly but the particles are about 20 times smaller than a red blood cell. Image courtesy of Hui Wang, M.S., Rice University.