Near-infrared narrow-band imaging of gold/silica nanoshells in tumors.

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.

Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model.

We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)-absorbing, 150-nm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 +/- 4.1 degrees C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 +/- 1.1 degrees C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation.