Spatially controlled photothermal heating of bladder tissue through single-walled carbon nanohorns delivered with a fiberoptic microneedle device

Abstract

Laser-based photothermal therapies for urothelial cell carcinoma (UCC) are limited to thermal ablation of superficial tumors, as treatment of invasive lesions is hampered by shallow light penetration in bladder tissue at commonly used therapeutic wavelengths. This study evaluates the utilization of sharp, silica, fiberoptic microneedle devices (FMDs) to deliver single-walled carbon nanohorns (SWNHs) serving as exogenous chromophores in conjunction with a 1,064-nm laser to amplify thermal treatment doses in a spatially controlled manner. Experiments were conducted to determine the lateral and depth dispersal of SWNHs in aqueous solution (0.05mg/mL) infused through FMDs into the wall of healthy, inflated, ex vivo porcine bladders. SWNH-perfused bladder regions were irradiated with a free-space, CW, 1,064-nm laser in order to determine the SWNH efficacy as exogenous chromophores within the organ. SWNHs infused at a rate of 50μL/min resulted in an average lateral expansion rate of 0.36 ± 0.08cm(2)/min. Infused SWNHs dispersal depth was limited to the urothelium and muscular propria for 50μL/min infusions of 10min or less, but dispersed through the entire thickness after a 15-min infusion period. Irradiation of SWNH-perfused bladder tissue with 1,064nm laser light at 0.95W/cm(2) over 40s exhibited a maximum increase of approximately 19°C compared with an increase of approximately 3°C in a non-perfused control. The results indicate that these silica FMDs can successfully penetrate into the bladder wall to rapidly distribute SWNHs with some degree of lateral and depth control and that SWNHs may be a viable exogenous chromophore for photothermal amplification of laser-based UCC treatments.