Single-walled nanotubes-cylinders of carbon about a nanometer in diameter-have
been highly touted for potential applications such as ultrastrong fibers, electrical
wires in molecular devices, or hydrogen storage components for fuel cells. Thanks
to a new development by researchers at the National
Institute of Standards and Technology (NIST) and five partners, you can
add one more application to the list: detection and destruction of an aggressive
form of breast cancer.
Photomicrographs demonstrate the dramatic impact of using nanotubes to selectively locate and destroy HER2 breast cancer tumors. Tumor cells on the left were treated only with antibodies against the HER2 protein and then irradiated with near-infrared light. Those on the right were treated with a complex of antibodies and nanotubes and then irradiated. Both cultures then were stained with fluorescent dye-green color indicates live cells while red marks areas where cells have been killed. Credit: NIST
HER2 is one of a family of genes that help regulate the growth and proliferation
of human cells. Normal cells have two copies of HER2, but about 20 to 25 percent
of breast cancer cells have multiple copies of the gene, resulting in the overproduction
of a HER2-encoded protein (called HER2 and designated in Roman type versus italics
for the gene) that is associated with particularly fast growing and difficult
to treat tumors. About 40,000 women in the United States are diagnosed annually
with this form of breast cancer.
In a recently published paper in BMC Cancer,* the NIST-led research team bonded
an antibody that has been created to attack the HER2 protein, chicken immunoglobulin
Y (IgY), to short nanotubes (about 90 nanometers long, or 5,000 times shorter
than an amoeba). Both halves of the special combination-the antibody and the
nanotube-have critical roles to play in selectively hunting down the HER2 tumor
cells and eliminating them.
First, the broad genetic differences between avian and human species means
that the chicken IgY antibody to HER2 reacts strongly with the target protein
expressed on tumor cells while ignoring normal cells with other human proteins.
The carbon nanotubes attached to the antibodies also become linked to the HER2
tumors.
Two unique optical properties of carbon nanotubes allow this link to be exploited
for improved detection and destruction of HER2 breast cancer cells. Near-infrared
laser light at a wavelength of 785 nanometers reflects intensely off the nanotubes,
and this strong signal is easily detected by a technique called Raman spectroscopy.
Increase the laser light's wavelength to 808, nanometers and it will be
absorbed by the nanotubes, incinerating them and anything to which they're
attached-in this case, the HER2 tumor cells.
The experiment described in the BMC Cancer paper was conducted in laboratory
cell cultures. Using the HER2 IgY-nanotube complex to selectively identify and
target HER2 tumors resulted in a nearly 100 percent eradication of the cancer
cells while nearby normal cells remained unharmed. In comparison, there only
was a slight reduction in cancer cells for cultures treated with anti-HER2 antibody
alone.
The next step for the research team is to conduct mouse trials of the HER2
IgY-nanotube complex to see if the dramatic cancer-killing ability works in
animals as well as it does in the lab. In a separate but related project, the
team hopes to use a nanotube-antibody combination against another tumor cell
protein, MUC4, to treat pancreatic cancer.
The research was funded under an interagency agreement between NIST and the
National Cancer Institute (NCI), and in part by a grant from the National Science
Foundation. Along with scientists from NIST, the research team included members
from Rutgers University, Cornell University, the New Jersey Institute of Technology,
NCI and Translabion, a private company located in Clarksburg, Md.
* Y. Xiao, X. Gao, O. Taratula, S. Treado, A. Urbas, R.D. Holbrook, R.E. Cavicchi,
C.T. Avedisian, S. Mitra, R. Savla, P.D. Wagner, S. Srivastava and H. He. Anti-HER2
IgY antibody-functionalized single-walled carbon nanotubes for detection and
selective destruction of breast cancer cells. BMC Cancer, Vol. 9, No. 351, published
online Oct. 2, 2009.