Selective nanoparticle‐directed ablation of the canine prostate

Abstract

Prostate cancer is the most frequent cancer type and the second most common cause of cancer death among US men. This study, adapted a previously reported nanoparticle-directed photothermal treatment of brain tumors to the treatment of prostate disease by using normal canine prostate in vivo, directly injected with a suspension of nanoparticles as a proxy for prostate tumor, and by developing laser dosimetry for prostate which is marginally ablative in native tissue, yet producing photothermal coagulation in prostate tissue containing nanoparticles. Canine prostates were exposed by surgical laparotomy and directly injected with suspensions of nanoparticles (nanoshells) and irradiated by a NIR laser source delivered percutaneously by an optical fiber catheter and isotropic diffuser. The photothermal lesions were permitted to resolve for up to 8 days, at which time each animal was euthanized, necropsied, and the prostate taken for histopathological and elemental analysis. Nanoparticles were retained for up to 4 hours in prostate and served as a proxy for prostate tumor. A marginally ablative laser dose of 3.0 W for 3 minutes was developed which would yield 4 mm-radius coagulo-necrotic lesions if nanoparticles were present. We have shown that the addition of nanoshells to native tissue, combined with a marginally ablative laser dose can generate ablative thermal lesions, and that the radial extent of the thermal lesions is strictly confined to within ∼4 mm of the optical fiber with sub-millimeter uncertainty. This, in turn, suggests a means of precise tumor ablation with an ability to obviate damage to critical structures limited primarily by the precision with which the optical fiber applicator can be placed. In so doing, it should be possible to realize a precise, nerve bundle and urethra sparing prostate cancer treatment using a minimally invasive, percutaneous approach.