Abstract 5523: Gold nanoshells in the treatment of high-grade gliomas in a mouse model

Abstract

Abstract Purpose: To evaluate the anti-tumor activity of near-infrared (NIR) absorbing gold-silica nanoshells against high grade gliomas in an in vivo subcutaneous mouse model. Background: Nanoshells with a silica core and a gold outer layer, which are optically tunable with peak absorption between 790 and 810 nm, have been shown to preferentially accumulate in colon cancer models after i.v. administration as a result of the enhanced vascular permeability and retention effect. When the tumor is illuminated with NIR light, the gold nanoshells are thermally activated. This results in tumor ablation without damage to normal tissues, since NIR light is not appreciably absorbed by tissue components at these wavelengths. High-grade gliomas are an attractive target for this type of therapy because the vast majority of tumors remain incurable with multi-modality therapeutic approaches, with local control being the primary manifestation of disease progression or recurrence. Methods: Gold silica nanoshells were synthesized according to previously published procedures. Survival studies were performed in NOD SCID mice with subcutaneous U373 glioma tumors in the right hind flank. When the tumor diameter was 3-5 mm, either 100 µl of PEG-coated nanoshells (treatment group, n =7) or 100 µl of saline (control group, n=8) were injected via tail vein. Twenty-four hours later tumors were exposed to an 808 nm diode laser at 4 W/cm2 for 3 minutes. Mice were monitored daily following treatment and euthanized when tumors reached 10 mm in largest diameter. Results: In the subcutaneous xenografts the overall survival at 90 days was 57% in the treatment group and 0% in the control group. None of the control group mice survived past 24 days. In addition, all of the mice in the treatment group that were still alive at 90 days were completely tumor-free without any sign of recurrence. Conclusions: These studies demonstrate that gold nanoshells can accumulate in subcutaneous glial tumors at levels sufficient to improve survival following thermal activation with NIR light. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5523.