20 Apr 2007
US researchers have shown that gold nanorods can enable two-photon luminescence imaging to detect early-stage cancer in skin cells.
The two-photon imaging technique, developed by Adela Ben-Yakar and colleagues at the University of Texas at Austin, exploits gold nanorods as contrast agents that improve the image brightness and so could allow body tissue to be probed to a greater depth than before.
More than 85% of all cancers begin in epithelial cells, which line both the skin and the cavities inside the body, but epithelium tissue can be as thick as 500 µm in humans. Two-photon imaging is already established as a powerful technique for detecting cancer because it allows non-invasive imaging of subcellular features that lie hundreds of microns deep inside tissue, but brighter images would allow for more accurate diagnosis.
Scientists have therefore started to investigate new classes of luminescent contrast agents, such as quantum dots and metallic nanoparticles, to improve the technique. However, most quantum dots contain heavy metals that are cytotoxic, making them unsuitable for clinical applications.
In contrast, gold nanoparticles are not only biocompatible, but Ben Yakar and colleagues have also shown that their use can produce images nearly 4000 times brighter than those obtained from autofluorescence.
The researchers began by preparing gold nanorods that were around 50 nm long and 15 nm wide. Next, they used the rods to label skin cancer cells embedded in a collagen matrix, which mimics the cells in tissue.
The researchers then imaged the cells using a home-built inverted multiphoton microscope. They excited the cells at 760 nm and observed the two-photon luminescence -- produced when two photons are absorbed by a nanorod at the same time -- from the cells.
The team found that the luminescence from the rods was more than 4000 times brighter than the two-photon autofluorescence from unlabelled cancer cells. Moreover, the technique was able to image tissue down to 75 µm deep.
"This bright two-photon contrast agent could provide the ability to detect and diagnose cancer in its very early stages because it can image the whole epithelium layer," Ben-Yakar told nanotechweb.org. "At present, there is no other optical-molecular imaging technique than can do this and provide information at the micron resolution."
The researchers say they are now building a new upright microscope that will allow them to image even deeper. Indeed, their goal is to image tissue down to 500 µm. The gold nanorods could also be used in cancer therapy and the Texas team eventually plans to incorporate plasmonic laser ablation into their imaging technique to eliminate any cancer cells detected. Here, a nanorod would act as a nano-lens that would focus the light to the near-field of the particle and allow ablation of cancer cells with much more precision than is possible with thermal techniques.
"We'll be able image deep and then remove the cancer cells without heating the surrounding tissue," said Ben-Yakar.