Abstract. The photothermal ablation of solid tumors using exogenous, near-infrared ͑NIR͒-absorbing nanoparticles has been previously investigated using various preclinical models and is currently being evaluated in the clinic. Here, we evaluate the circulation kinetics, preliminary toxicity, and efficacy of photothermal ablation of solid tumors using gold nanorods systemically delivered and passively accumulated in a murine subcutaneous colon cancer model. Tumored animals were infused with nanorods followed by the percutaneous illumination of the tumor with an 808-nm laser. Control groups consisted of laser-only, nanorod-only, and untreated tumored animals. The survival of the treated and control groups were monitored for 60 days post-treatment. The survival of the photothermally treated group was statistically longer than the control groups, with approximately 44% tumor free through the evaluation period. Histopathology of the major organs of animals infused with nanorods did not indicate any significant toxicity at 60 days post-treatment. Particle biodistribution was evaluated by elemental analysis of the major organs of untumored mice at 1, 7, and 30 days after infusion with nanorods. Elemental analysis indicates nanorod clearance from the blood and retention by the reticuloendothelial system. This study indicates that gold nanorods are promising agents for photothermal ablation of solid tumors.
Abstract. In this study, high resolution backward-mode photoacoustic microscopy ͑PAM͒ is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. PAM takes advantage of the strong near-infrared absorption of nanoshells and their extravasation tendency from leaky tumor vasculatures for imaging. Subcutaneous tumors are grown on immunocompetent BALB/c mice. Polyethylene glycol ͑PE-Gylated͒ nanoshells with a peak optical absorption at ϳ800 nm are intravenously administered. With an 800-nm laser source, a prescan prior to nanoshell injection is taken to determine the background that is free of nanoshell accumulation. After injection, the 3-D nanoshell distribution at the tumor foci is monitored by PAM for 6 h. Experimental results show that accumulated nanoshells delineate the tumor position. Nanoshell accumulation is heterogeneous in tumors: more concentrated within the tumor cortex and largely absent from the tumor core. Because nanoshells have been recently demonstrated to enhance thermal therapy of subcutaneous tumors, we anticipate that PAM will be an important aid before, during, and after nanoshell thermal therapy. Photoacoustic imaging is an emerging noninvasive imaging modality and has been shown to be a promising tool for visualizing tissue structures and functions by means of laserinduced ultrasound.1,2 Structures with high optical absorption, such as blood vessels in the visible spectral region, can be imaged with ultrasound resolution, which is not limited by the strong optical scattering in biological tissues. Recently, an invivo backward-mode confocal photoacoustic microscope ͑PAM͒ with dark-field illumination was invented to image microvasculatures in the skin. [3][4][5] This system offers high lateral resolution ͑45 m at the focal point͒, high axial resolution ͑ϳ15 m͒, and is capable of imaging optical absorption contrast as deeply as 3 mm. It shows great potential for applications in dermatology and related cancer research. Contrast-agent-enhanced optical imaging techniques possess high sensitivity and specificity. In this study, we use gold nanoshells ͑AuroShell™ Particles, Nanospectra Biosciences, Incorporated, Houston, Texas͒ as a contrast agent for photoacoustic microscopy of tumors. Gold nanoshells have been applied to photothermal therapy of subcutaneous murine tumors 6 and have also been used as a contrast agent for invivo brain imaging with photoacoustic tomography, enhancing contrast of cortex vessels in rat brain.7 Gold nanoshells are a new type of optically tunable nanoparticles, composed of silica cores ͑ϳ116 nm in diameter͒ coated with an ultrathin gold shell ͑ϳ14 nm͒.8 By adjusting the core size relative to the thickness of the gold shell, the optical properties of nanoshells can be varied across a broad range of the electromagnetic spectrum that spans the visible and infrared regions. In our cancer applications, gold nanoshells are designed to absorb light at near-infrared ͑NIR͒ wavelengths. The peak optical absorption of nanos...
Gold nanoshells (GNS) are a new class of nanoparticles that can be optically tuned to scatter or absorb light from the near-ultraviolet to near-infrared (NIR) region by varying the core (dielectric silica)/shell (gold) ratio. In addition to spectral tunability, GNS are inert and bioconjugatable, making them potential labels for in vivo imaging and therapy of tumors. We report the use of GNS as exogenous contrast agents for enhanced visualization of tumors using narrow-band imaging (NBI). NBI takes advantage of the strong NIR absorption of GNS to distinguish between blood and nanoshells in the tumor by imaging in narrow wavelength bands in the visible and NIR, respectively. Using tissue-simulating phantoms, we determined the optimum wavelengths to enhance contrast between blood and GNS. We then used the optimum wavelengths for ex vivo imaging of tumors extracted from human colon cancer xenograft bearing mice injected with GNS. Systemically delivered GNS accumulated passively in tumor xenografts by the enhanced permeability and retention (EPR) effect. Ex vivo NBI of tumor xenografts demonstrated heterogeneous distribution of GNS with a clear distinction from the tumor vasculature. The results of this study demonstrate the feasibility of using GNS as contrast agents to visualize tumors using NBI.
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