Abstract C99: Panitumumab conjugated gold nanoparticles induce hyperthermic cytotoxicity in pancreatic carcinoma cell lines after noninvasive radiofrequency field exposure

Abstract

Abstract Introduction: Many cancer cells that highly express epidermal growth factor receptor-1 (EGFR-1) have been demonstrated to endocytose antibody specific targeted nanoparticles such as cetuximab conjugated gold nanoparticles. These gold nanoparticles are subsequently delivered throughout the cell. When gold nanoparticles are exposed to near infrared laser (NIR) radiation or non-invasive radiofrequency fields, they heat in a concentration dependent manner. Radiofrequency (RF) fields are advantageous because they easily penetrate through body tissues without injury. We investigated the effects of a clinically available EGFR-1 antibody, panitumumab, conjugated to gold nanoparticles in noninvasive RF fields. Methods: Solid gold nanoparticles (10 nm) were covalently linked to panitumumab, a monoclonal antibody against EGFR-1. Two pancreatic carcinoma cell lines, Panc-1 and Capan-1, were treated with 200 nM panitumumab linked gold nanoparticles in media for four hours. After replacing the media with fresh media not containing the antibody linked gold nanoparticles, the cells were exposed to an RF field at a generator power of 600W for a total of 3 minutes. The media temperature was kept below 42°C in order to prevent non-specific apoptosis. Viability and apoptosis were evaluated with flow cytometry three days later. Statistical analysis was performed with the Student's t-test and uncertainties represent standard errors of the mean. Results: The viability of control cells not treated with the conjugate remained greater than 90% for both cell lines. The antibody-nanoparticle conjugate alone decreased the viability of Panc-1 cells to 81.0% ± 1.1%. However, after RF field exposure, the viability decreased to 57.2% ± 7.9% (p < 0.03). After antibody-conjugate treatment, Capan-1 cells viability was 89.5% ± 3.9%. After RF field exposure, however, the viability decreased to 67.8% ± 3.8% (p <0.03). Conclusions: The susceptibility of pancreatic carcinoma cell lines to gold nanoparticle mediated noninvasive RF field hyperthermic therapy may be related to the combined effects of monoclonal antibody treatment and intracellular hyperthermia. Based on this simple model, it appears that there is a relationship between EGFR-1 expression, cytotoxicity associated with monoclonal antibody therapy, and hyperthermic cytotoxicity after RF field exposure. Combined rational therapy utilizing non-invasive RF fields may provide for opportunities where traditional radiotherapy has failed and NIR therapy is not readily possible due to tumor location deep within a body cavity. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C99.