Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model
We report on a pilot study demonstrating 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 photo-thermal
ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID
mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of
near-infrared absorbing, 150 nm nanoshells was infused intravenously 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 neo-vasculature represented an interruption of the normal blood-brain barrier.
Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared 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±4.1ºC. Identical laser
doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of
48.6±1.1ºC. 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. Post-mortem histopathology of
treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.
This paper was published in SPIE Proceedings Vol. 7161