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.

Single-Molecular Near-Infrared-II Theranostic Systems: Ultrastable Aggregation-Induced Emission Nanoparticles for Long-Term Tracing and Efficient Photothermal Therapy

“…It illustrates that mice without receiving photothermal treatment might not be so healthy due to the rapid tumor growth. It is worth mentioning that the reports about in vivo photothermal treatment on orthotopic tumor model were very rare , due to the lack of efficient imaging modality for precise localization of deep tumor sites. With assistance of the NIR-II fluorescence signals from BPN-BBTD NPs, deep-tissue and high-resolution imaging guided photothermal treatment on in vivo orthotopic tumors was first achieved by using AIEgens.…”

“…It illustrates that mice without receiving photothermal treatment might not be so healthy due to the rapid tumor growth. It is worth mentioning that the reports about in vivo photothermal treatment on orthotopic tumor model were very rare 54,55 Although the orthotopic tumors were not completely eradicated because of the scattering attenuation of 785 nm laser irradiation in biological tissues, the growth was indeed suppressed upon the thermal ablation. In our future work, the wavelength and intensity of irradiation laser will be optimized to further improve the photothermal therapeutic effect.…”

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

“…BC is often characterized by a high mutation rate and high EGFR expression in approximately 50% of cases (Colquhoun and Mellon, 2002 ). Thanks to the expression of EGRF on BC cells, an anti-EGFR monoclonal antibody conjugated to gold nanorods was able to effectively bind EGFR-expressing BC cells and reduce the systemic exposure and clearance of nanoparticles from the body (Yang et al, 2015 ). These results indicate the use of monoclonal antibodies represents another possible approach for delivery of molecules to specific tissues.…”

A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer

“…Orthotopic cancer models closely resemble canonical bladder cancer development 32 and thus appear to be more suitable than heterotopic models for recapitulating the clinical HIVEC treatments. There are several methods to simulate HIVEC in animal models, such as conductive heating 25 , 33 , 34 , radiofrequency induced hyperthermia (RF-HT) 35 – 38 , magnetic nanoparticles 26 , 39 , photothermal ablative therapy 40 , 41 , and high intensity focused ultrasound (HIFU) 24 , 42 . These techniques vary in technical complexity and compatibility with orthotopic tumour models (Table 1 ).…”