Gold Nanorods Detect Ovarian Cancer, Improve Surgical Removal in Mice
Using gold nanorods that are visible using two different types of imaging techniques, researchers at the Stanford University Center for Cancer Nanotechnology Excellence and Translation (Stanford CCNE-T) have developed a promising new method that may be able to detect early stage ovarian cancer and help surgeons completely remove the detected tumor. The researchers have successfully tested this imaging agent in an animal model of human ovarian cancer and are already working on an improved agent that may be able to discriminate between malignant and benign ovarian masses. The Stanford CCNE-T team, led by Sanjiv Sam Gambhir, reported its findings in the journal ACS Nano.
Ovarian cancer is the fifth most common cancer among women, and it causes more deaths than any other type of female reproductive cancer, largely because ovarian cancer symptoms are vague and it most often goes undiagnosed until it has spread to other parts of the body. However, when detected early, the five-year survival rate is as high as 95 percent, so the development of non-invasive and inexpensive technology to detect early stage ovarian cancer could have a profound impact on patient survival.
To create their new imaging agent, Dr. Gambhir’s team took advantage of the unique properties of gold nanorods, which interact strongly with light in a variety of useful ways. For example, gold nanorods will absorb near-infrared light and produce heat that creates a pressure wave that can be detected with standard ultrasound devices that are already used widely in doctor’s offices. This technique is known as photoacoustic spectroscopy. Gold nanorods will also generate a well-defined optical emission that can be detected using surface-enhanced Raman spectroscopy (SERS), another well-established measurement technology.
Another useful property of nanorods in general is that their shape somehow enables them to accumulate more effectively than spherical particles around tumors. Researchers assume that the long, thin shape enables the rods to more easily penetrate and escape the leaky blood vessels that surround tumors.
To assess the imaging capabilities of gold nanorods, the investigators created three different batches that varied in the ratio of their length to width, also known as the aspect ratio. Based on the intensity of the photoacoustic signal and the Raman signal, the researchers settled on a gold nanorod with an aspect ratio of 3.5 (756 nm absorbance) for further testing. When injected intravenously into mice bearing human ovarian tumors, these gold nanorods were readily detected through the skin in and around tumors in live animals. The researchers noted that the photoacoustic signal from the injected nanorods remained stable for three days, while signal from nanorods circulating in blood returned to baseline levels within 24 hours, a desirable trait for a clinically useful imaging agent.
Next, Dr. Gambhir and his colleagues used the SERS signal to guide surgical removal of the tumors. Presurgical images clearly showed the location and edges, or margins, of even small tumors, and post-surgical imaging confirmed that all traces of tumor were removed.
Though the photoacoustic signal from the gold nanorods can be detected through as much as 4 centimeters (just over 1.5 inches) of tissue, Dr. Gambhir and his colleagues are developing photoacoustic catheters that will further increase the number of accessible sites. They are also developing nanorods targeted specifically to malignant ovarian tumors that would not only accumulate better in tumors, but may also be able to distinguish malignant from benign ovarian masses.
This work, which is detailed in a paper titled, “Gold nanorods for ovarian cancer detection with photoacoustic imaging and resection guidance via Raman imaging in living mice,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.View abstract