Presentation Abstract

Abstract Number: 2728
Presentation Title: Thermal ablative therapy with novel gold nanorods in an orthotopic model of urinary bladder cancer
Presentation Time: Monday, Apr 07, 2014, 1:00 PM - 5:00 PM
Location: Hall A-E, Poster Section 33
Poster Board Number: 29
Author Block: Xiaoping Yang1, Lih-Jen Su1, Francisco G. La Rosa1, Elizabeth Erin Smith1, Suehyun Katherine Cho2, Brian Kavanagh1, Won Park2, Thomas W. Flaig1. 1Univ. of Colorado Denver Anschutz Medical Campus, Aurora, CO; 2Univ. of Colorado at Boulder, Aurora, CO
Abstract Body: 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.
Conclusions
Photothermal ablation with EGFR-directed gold nanorods is effective and well tolerated in an in vivo model of urinary bladder cancer. Future clinical development would include NIR light delivery via a cystoscope in a human application
Summary of luciferase results of in vivo photothermal treatment
Total miceLuciferase DecreaseLuciferase IncreaseLuciferase No Significant Change
Conjugated Nano Rods+Laser161303
Laser Only14275