With clinical trials for photothermal tumor ablation using laser-excited tunable plasmonic nanoparticles already underway, increasing understanding of the efficacy of plasmonic nanoparticle-based photothermal heating takes on increased urgency. Here we report a comparative study of the photothermal transduction efficiency of SiO₂/Au nanoshells. Au₂S/Au nanoshells, and Au nanorods, directly relevant to applications that rely on the photothermal response of plasmonic nanoparticles. We compare the experimental photothermal transduction efficiencies with the theoretical absorption efficiencies for each nanoparticle type. Our analysis assumes a distribution of randomly oriented nanorods, as would occur naturally in the tumor vasculature. In our study, photothermal transduction efficiencies differed by a factor of 3 or less between the different types of nanoparticle studied. Both experiment and theory show that particle size plays a dominant role in determining transduction efficiency, with larger particles more efficient for both absorption and scattering, enabling simultaneous photothermal heating and bioimaging contrast enhancement.

AIMS:
The treatment efficacy of laser-induced thermal therapy is greatly enhanced by the presence gold coated nanoshells within the tissue being treated. The nanoshells are turned to exhibit a surface plasmon resonance at the frequency of the incident laser light, dramatically increasing the therapeutic efficiency of the laser treatment. Accurate modeling of the resulting temperature distributions is essential for treatment planning. Analytic solutions are desirable because they give greater insight into the physical meaning of the different terms that contribute to the problem.

METHODS:
The heat equation is solved by application of the Green’s function method and the solution is compared to experimental temperature data for gel phantoms containing different concentrations of nanoshells. The experimental temperature data was obtained by using magnetic resonance temperature imaging methods while the gel was being heated with an 810 nm laser.

RESULTS:
Reasonable agreement was obtained between the results of the analytic calculation and the experimental data for the various concentrations of nanoshells and laser outputs tested. This agreement was consistent for both the spatial and temporal domain. On average the disagreement between analytical calculation and experiment was 0.93+/-0.84 degrees C.

CONCLUSION:
We have shown that analytic solutions to the heat equation using the Green’s function approach can be used to describe experimental temperature distributions due to the presents of nanoshells for various laser powers and nanoshell concentrations.

We report noninvasive modulation of in vivo tumor radiation response using gold nanoshells. Mild-temperature hyperthermia generated by near-infrared illumination of gold nanoshell-laden tumors, noninvasively quantified by magnetic resonance temperature imaging, causes an early increase in tumor perfusion that reduces the hypoxic fraction of tumors. A subsequent radiation dose induces vasculardisruption with extensive tumor necrosis. Gold nanoshells sequestered in the perivascular space mediate these two tumor vasculature-focused effects to improve radiation response of tumors. This novel integrated antihypoxic and localized vascular disrupting therapy can potentially be combined with other conventional antitumor therapies.

The detection of a gold nanoparticle contrast agent is demonstrated using a photothermal modulation technique and phase sensitive optical coherence tomography (OCT). A focused beam from a laser diode at 808 nm is modulated at frequencies of 500 Hz-60 kHz while irradiating a solution containing nanoshells. Because the nanoshells are designed to have a high absorption coefficient at 808 nm, the laser beam induces small-scale localized temperature oscillations at the modulation frequency. These temperature oscillations result in optical path length changes that are detected by a phase-sensitive, swept source OCT system. The OCT system uses a double-buffered Fourier domain mode locked (FDML) laser operating at a center wavelength of 1315 nm and a sweep rate of 240 kHz. High contrast is observed between phantoms containing nanoshells and phantoms without nanoshells. This technique represents a new method for detecting gold nanoparticle contrast agents with excellent signal-to-noise performance at high speeds using OCT.

PURPOSE:
Laser activated gold nanoshell thermal ablation represents a new, minimally invasive technology that offers benign tissue sparing thermal ablation of malignant tumors. We evaluated the efficacy of this technology for eradicating prostate cancer in a subcutaneous tumor model.

MATERIALS AND METHODS:
The 110 nm gold nanoshells with a 10 nm gold shell are designed to act as intense near infrared absorbers. PC-3 cells were injected on the dorsum of nude mice in 3 groups, including 1-gold nanoshell plus near infrared laser, 2-saline alone and 3-near infrared laser alone. Animals received 7.0 ml/gm body weight (low dose) or 8.5 ml/gm body weight (high dose) nanoshells via tail vein injection. Control animals received saline. A 810 nm near infrared laser with a 200 mu laser fiber and an energy setting of 4 W/cm(2) was aimed at the tumor bed for 3 minutes. Tumors were measured at days 0, 7, 14 and 21. Tissue temperature was monitored during laser activation. Tumors were harvested at day 21 and stained with hematoxylin and eosin, and for nicotinamide adenine dinucleotide diaphorase activity.

RESULTS:
We observed 93% tumor necrosis and regression in the high dose treated group. Nicotinamide adenine dinucleotide staining corroborated this finding. The ablation zone was sharply limited to the laser spot size. There was no difference in the size or tumor histology in control groups, indicating a benign course for near infrared laser treatment alone. Temperatures up to 65.4C were attained in the treated group.

Gold nanoshells (dielectric silica core/gold shell) are a novel class of hybrid metal nanoparticles whose unique optical properties have spawned new applications including more sensitive molecular assays and cancer therapy. We report a new photo-physical property of nanoshells (NS) whereby these particles glow brightly when excited by near-infrared light. We characterized the luminescence brightness of NS, comparing to that of gold nanorods (NR) and fluorescent beads (FB). We find that NS are as bright as NR and 140 times brighter than FB. To demonstrate the potential application of this bright two-photon-induced photoluminescence (TPIP) signal for biological imaging, we imaged the 3D distribution of gold nanoshells targeted to murine tumors.