Abstract A30: Targeting of the mTOR pathway in human acute myeloid leukemia cells using functionalized gold nanoparticles

Abstract

Abstract Specific targeting of fundamental biochemical/signaling pathways in human malignant cells with the purpose of recognition and delivery of cytotoxic drugs into them is a very promising but not well-developed strategic approach. It is a major focus of current molecular cancer research, nanomedicine, biotechnology, and synthetic biology. mTOR pathway is a master regulator of metabolism and cell growth in the majority of malignant cells. Especially this applies to cancerous myeloid cells where it determines the ability of the cells to survive and evade the host immune surveillance. Therefore, specific targeting of this pathway could be a novel strategy for treatment of acute myeloid leukemia (AML), a blood/bone marrow cancer that can rapidly progress into a systemic and often fatal malignancy. In this study we demonstrated for the first time a fundamentally novel approach for specific targeting of human AML cells by functionalized gold nanoparticles. The immune receptor Tim-3 is highly expressed in human AML cells. It is one of the key members of the Tim-3/galectin-9 autocrine pathway that plays a pivotal role in AML cell survival and immune evasion (1). Rapamycin inhibits the mTOR activity, thus affecting translational pathways in AML cells. Inhibition of the mTOR leads to a rapid killing of AML cells. Using these nanomaterials, we managed to successfully deliver rapamycin into AML cells, reaching attenuation of the mTOR activity. Concentration of rapamycin required to reach such a strong effect was at least 50 times lower compared to that of free rapamycin required to achieve the similar result. We therefore concluded that our technology is of potential use for specific targeting of AML cells for the purpose of diagnosis and possibly therapy (2). The nanoconjugates developed in our work can be used to specifically identify malignant blood cells, thus allowing rapid and robust AML diagnosis. Citation Format: Inna M. Yasinska, Bernhard F. Gibbs, Luca Varani, Rohanah Hussain, Giuliano Siligardi, Elizaveta Fasler-Kan, Luigi Calzolai, Vadim V. Sumbayev. Targeting of the mTOR pathway in human acute myeloid leukemia cells using functionalized gold nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A30.