Abstract 2728: Thermal ablative therapy with novel gold nanorods in an orthotopic model of urinary bladder cancer

2014 
Background The use of nanoparticles has shown great therapeutic potential, but delivery and clearance concerns have limited their use systemically. Intravesical instillation of nanoparticles in the urinary bladder provides a unique administration route to treat superficial bladder cancer. We examined the anti-tumor effect of epidermal growth factor receptor (EGFR)-directed gold nanorods combined with photothermal treatment in a superficial bladder cancer model. Methods A novel orthotopic nu/nu murine xenograft model was established through intravesical instillation of T24 human bladder cancer cells labeled with Luciferase. After confirmation of positive tumor cell implantation via bioluminescence, gold nanorods linked to the anti-EGFR antibody C225 were instilled into the bladder cavity. The nanorods were specifically fashioned to respond to near infrared (NIR) light, which was externally administered via an 808 nm diode laser to the bladder. A safe and effective regimen of in vivo photothermal ablation was determined by optimizing the duration, power and distance from the tumor to the laser source. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner. Results The tumor implantation rate with the T24 human cancer cell was approximately 90%. The optimized regimen of photothermal treatment in this setting was laser power of 2.1 W/cm2 for 30 seconds at 2.5 centimeters from the skin. Using this in vivo tumor model, and near-infrared energy combined with C225-conjugated gold nanorods, we demonstrate significant therapeutic efficacy against the implanted orthotopic bladder tumor (Table) with minimal systemic toxicity using this regimen.
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