Combining Nanotubes and Antibodies for Breast Cancer 'Search and Destroy' Missions
Single-walled carbon nanotubes have been highly touted for their potential as novel delivery agents for cancer detection and therapeutic agents. Now, a team of investigators from six institutions have created a multifunctional carbon nanotube that can detect and destroy an aggressive form of breast cancer.
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 cancers consist of cells have multiple copies of the gene, resulting in the overproduction of a HER2-encoded protein 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 paper published in the journal BMC Cancer, the team led by Huixin He, Ph.D., of Rutgers University, and Yan Xiao, Ph.D., of the National Institute of Standards and Technology (NIST), described how it created the new dual-purpose nanostructure by attaching an anti-HER2 antibody to short carbon nanotubes. But rather than use a human anti-HER2 antibody, the investigators used an antibody raised in chickens. The distinct genetic differences between avian and human species enabled the chicken antibody to react strongly with the target protein expressed on tumor cells while ignoring normal cells with other human proteins.
The investigators then took advantage of two unique optical properties of carbon nanotubes to detect and then destroy 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 antibody-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 antibody-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, which is detailed in a paper titled, "Anti-Her2IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cels," was funded under an interagency agreement between NIST and the National Cancer Institute (NCI). Along with scientists from NIST and Rutgers, the research team included members from Cornell University, the New Jersey Institute of Technology, NCI and Translabion, a private company located in Clarksburg, Md. This paper is available at no charge at the journal's Web site.