Gold nanorods align to reveal cancer cells’ locations

Michael J. Lander

For targeting and revealing cancer cells, gold nanorods bound to antibodies may provide a useful tool. Led by Mostafa A. El-Sayed of Georgia Institute of Technology in Atlanta, researchers from this institution and from the University of California, San Francisco, have used the gold nanostructures to yield distinct spectroscopic signals from cancer cells. Their method could find application in diagnosis of the disease.

The scientists applied the concept of surface-enhanced Raman spectroscopy, in which the surfaces of nanoscale metal particles are used to increase the Raman signal of nearby molecules by several orders of magnitude. To start the experiment, they attached gold nanorods with a longitudinal absorption maximum at 800 nm (in the near-infrared) to monoclonal antibodies. The antibodies had an affinity for epidermal growth factor receptors, found to varying degrees on the surface of human cells. They then incubated the nanorod-antibody conjugates with nonmalignant epithelial cells and with malignant oral squamous cells.

Cancer cells bound with gold nanorod-carrying antibodies appear a reddish-gold color in this dark-field image. Courtesy of Mostafa A. El-Sayed, Georgia Institute of Technology.

To take bright- and dark-field images of the mixtures, the scientists used an Olympus inverted microscope. They collected Raman spectra of the samples with a microspectrometer from Kaiser Optical Systems Inc. during excitation from a diode laser operating at 785 nm. They gathered polarized spectra by rotating the specimen at intervals of 20° with respect to the laser’s electric field.
In dark-field images, especially, cancer cells appeared uniformly red because of increased growth factor expression. Antibodies attached themselves to the growth factors, carrying with them the strongly light-scattering nanorods. The conjugates did not bind to the healthy cells but rather appeared as widely dispersed red specks. Raman spectra showed the difference as well. Eighty percent of normal cells gave no spectra, and the remainder yielded only a weak signal. Cancer cells yielded either a strong or a very strong signal, corresponding to that of the gold nanorod’s capping molecule.

As reported in the May 3 online issue of Nano Letters, examination of data from the polarization experiments suggested that the nanorods align themselves in an organized fashion on the surface of cancer cells. This formation leads both to polarization dependence and to strong homogeneous surface plasmon fields, causing malignant cells to exhibit a strong and sharp signal. The pattern allows their clear differentiation from healthy cells, to which too few conjugates bind for alignment to occur.

By identifying signal characteristics unique to cancer cells, the researchers have opened the possibility of using the antibody-conjugated gold nanorods for accurate Raman-based cancer diagnosis. Because laser excitation also causes cancer cells bound with the aligned particles to heat up, the investigators are assessing the technique’s potential use as a thermal cancer therapy in small-animal studies.