The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

ABSTRACT

BACKGROUND: Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. OBJECTIVE: To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. METHODS: Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. RESULTS: The optimal approach for an individual treatment was 2.1 W/cm2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity (n = 16) compared to mice treated with laser alone (n = 14) at the end of the study (p = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels (p = 0.045). CONCLUSIONS: Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.