Abstract 851: Gold nanoparticle-mediated infrared hyperthermia reduces the radiotherapy dose required for tumor therapy

Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration (∼2cm). Previously large, 50-150nm gold nanoshells and nanorods that absorb well in the NIR have been used. Here we show that small AuNPs, that may penetrate tumors better, barely absorb at 800nm. However, when conjugated to antitumor antibodies, they are taken up by tumor cells, which catalytically aggregate them by enzyme degradation and pH effects, thus shifting their absorption to the NIR region thereby amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells; this reduces background heating in blood and non-targeted tissues thereby increasing specificity in contrast to constructs that are always NIR absorbing. We show that treatment of subcutaneous EGFR overexpressing human squamous cell carcinoma (A431) tumor xenografts with 15nm AuNPs conjugated with anti-EGFR and NIR resulted in complete tumor ablation with virtually no normal tissue (skin) damage. Further, using radioresistant mouse squamous cell carcinoma SCCVII xenografts, we have combined AuNP-mediated infrared heating with x-ray therapy to take advantage of the well-known synergy of hyperthermia and radiotherapy. Lipoic Acid modified 15nm AuNPs were injected intratumorally by convection-enhanced delivery (CED) followed by NIR and X-ray therapy. It was found that the dose required for control of 50% the tumors, 55Gy, could be reduced to Citation Format: James F. Hainfeld, Michael J. O9Connor, Lynn Lin, Daniel N. Slatkin, F. Avraham Dilmanian, Henry M. Smilowitz. Gold nanoparticle-mediated infrared hyperthermia reduces the radiotherapy dose required for tumor therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 851. doi:10.1158/1538-7445.AM2014-851