Gold nanoparticles are being developed for molecular detection, biological imaging and targeted drug delivery. It is desirable to combine them with imidazole because it is the reactive moiety of many biological molecules, according to J. Houston Miller and others at George Washington University in Washington and at the University of Texas M.D. Anderson Cancer Center in Houston. The researchers say that such nanoparticles can increase data acquisition speeds and reduce laser power required for in vivo detection. To prove it, they used near-IR surface-enhanced Raman spectroscopy to detect gold-imidazole nanoparticles in vitro and in vivo. Imidazole, in the center, interacts with two surrounding gold nanoparticles. Researchers showed that imidazole catalyzes gold nanoparticle assembly by direct participation. In the future, gold-imidazole nanoparticles may be used as biological probes. Reprinted with permission from J. Houston Miller. Copyright 2006 American Chemical Society. They mixed imidazole and gold nanoparticle solutions, and the gold-imidazole particles assembled themselves by adsorption. Because biological tissue absorbs little near-IR radiation, and the surface-enhanced Raman spectroscopy signal from imidazole exhibits a dramatic peak wavelength upon near-IR excitation, they examined the imidazole solution with near-IR Raman spectroscopy, but the signal was weak. Surface-enhanced Raman spectroscopy boosted the imidazole signal by a factor of 2 x 106. Above 1.9 μM, imidazole catalyzed gold nanoparticle aggregation. Nanoparticles with fewer aggregates have a high surface area, which improves their binding efficiency and accessibility to binding sites, resulting in a larger spectroscopic signal. Thus, lower concentrations of imidazole can be used when making gold-imidazole nanoparticles for use as biological probes. The investigators injected 300 μl of gold-imidazole nanoparticles into tumors in mice and collected the light 3 mm above the skin using a 7-mm-focal-length fiber optic probe to perform surface-enhanced Raman spectroscopy. Only the mice that were injected with the nanoparticles exhibited the imidazole peak. The researchers said that the apparatus was not designed for in vivo detection, but that it provided proof-of-principle. Besides establishing that this technique can be used in vivo, they eventually want to systemically deliver targeted nanoparticles using technology such as phage display vectors.