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.
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 tumor specific 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.
Given their tunable optical properties and high optical absorption and scattering cross sections, gold nanoshells (GNS) have been explored for a number of in vitro and in vivo imaging contrast and cancer therapy agents. While it has been shown that GNSs preferentially accumulate at the tumor site, little is known about the accumulation kinetics within the tumor. We demonstrate accumulation kinetics of GNSs in bulk tumors and histology slides using two-photon induced photoluminescence (TPIP) imaging. We found that GNSs had a heterogeneous distribution with higher accumulation at the tumor cortex. In addition, GNSs were observed in unique patterns surrounding the perivascular region. These results demonstrate that direct luminescence based imaging of metal nanoparticles provides high resolution and molecular specific multiplexed images.
Gold nanoshells 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. Specifically, we demonstrate
NS excited at 780 nm produce strong two-photon induced photoluminescence (TPIP). We characterized the
luminescence brightness of NS, comparing to that of fluorescein-labeled fluorescent beads (FB). We find that NS are 140
times brighter than FB. To demonstrate the potential application of this bright TPIP signal for biological imaging, we
imaged the 3D distribution of gold nanoshells targeted to murine tumors.
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