Abstract 3704: Gemtuzumab ozogamicin conjugated gold nanoparticles induce cell death in D1.1 leukemia cells when exposed to a radiofrequency field

Abstract

Abstract Introduction: Acute T-cell leukemia cells may express the marker CD33. Gemtuzumab is a monoclonal antibody against CD33, used clinically in combination with ozogamicin, a cytotoxic antibiotic, for treatment of acute leukemias. It has been previously demonstrated that gold nanoparticles delivered intracellularly and exposed to nonionizing radiofrequency (RF) fields induce hyperthermic cytotoxicity. RF fields are not cytotoxic without the presence of nanoparticles. The purpose of this experiment is to investigate cell death in cells treated with gemtuzumab ozogamicin conjugated to gold nanoparticles after RF field exposure. Methods: D1.1 (acute T-cell leukemia) cells were plated in 60mm cell culture dishes. Two groups (n=3 in each group) of plated cells were treated for two hours with gemtuzumab ozogamicin conjugated to 10nm solid gold nanoparticles in media. One group of cells was then exposed to a radiofrequency field for a total generator energy of 1500 W-minutes. The control cells were treated with the same gold conjugate, but were not exposed to an RF field. Two days later, cell viability, apoptosis, and death was determined by flow cytometry. The groups were compared with Student's t-test. Results: RF fields induced apoptosis in 58.7% ± 3.95% of treated cells, compared with 8.66% ± 0.56% of the controls (p=0.002). The viability after RF exposure was 13.9% ± 6.11% while gemtuzumab ozogamicin gold conjugate alone decreased viability to 74.2% ± 0.85% (p=0.003). The temperature of the media was kept below 40°C to avoid nonspecific cell injury. Conclusions: Multimodality therapy (chemotherapy and nanoparticle-mediated hyperthermia) induced significantly more death in acute T-cell leukemia cells than antibody-chemotherapy alone. Antibodies specific to molecular targets on cells permit targeting of the heat mediator (nanoparticles) while preventing non-specific delivery of both nanoparticles and chemotherapeutic agent. The use of non-invasive RF fields to specifically induce cell death by hyperthermia with nanoparticles may present new options for the treatment of leukemias. 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 3704.