Image-guided molecular photothermal therapy using targeted gold nanoparticles acting as photoabsorbers can be used to noninvasively treat various medical conditions including cancer. Among different types of gold nanoparticles, gold nanorods are an attractive candidate for both photothermal therapy and photoacoustic imaging due to their high and tunable optical absorption cross-section. However, nanorods are not thermodynamically stable; under laser exposure, the nanorods can easily transform to spheres, thus changing their desired optical properties. In this study, gold-silica coreshell nanorods were prepared by coating silica directly onto the surface of PEGylated gold nanorods using a modified StÃÂ¶ber method. The nanorods were exposed to 800 nm wavelength, 7 ns pulses of light at a 10 Hz pulse repetition rate. For different fluences ranging from 0 to 8 mJ/cm2, the optical extinction spectrum was measured before and after the exposure to investigate their photothermal stability. Finally, the effectiveness of gold-silica core-shell nanoparticles as a photoacoustic contrast agent and photothermal nanoabsorber was tested using inclusion-embedded phantoms and a combined ultrasound and photoacoustic imaging system. The results of our study suggest that gold-silica core-shell nanorods are excellent candidates for image-guided molecular photothermal therapy.© (2010) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.