PO-409 Highly specific targeting of human acute myeloid leukaemia (AML) cells using functionalised gold nanoparticles

Abstract

IntroductionHighly specific targeting of human malignant cells with the purpose of recognition and delivery of specific drugs into them is a very promising but not well developed complex of diagnostic and therapeutic strategies. It is a major focus of current molecular cancer research, Nanomedicine, Biotechnology and Synthetic Biology.Material and methodsTHP-1 and primary human AML cells were used in our work. We constructed a complex, where 5 nm AuNPs carried a 27 kDa single chain antibody against T cell immunoglobulin and mucin domain 3 (Tim-3) in the ratio – 1 AuNP: 1 antibody molecule. The rest of the gold surface was covered with rapamycin immobilised in the form of glutathione-SH ester. Transmission electron microscopy and synchrotron radiation circular dichroism spectroscopy were used to characterise nanomaterials. Western blot analysis, FACS, in cell Western and ELISA were used to conduct experiments.Results and discussionsIn this study we demonstrated for the first time a new approach for highly specific targeting of human AML cells by functionalised gold nanoconjugates. The immune receptor Tim-3 is highly expressed in human AML cells. It is one of the key components of Tim-3/galectin-9 secretory pathway which is crucial for survival of malignant cells since it determines their ability to escape host immune surveillance.1 Thus, Tim-3 can be used as a target for specific recognition of AML cells. Rapamycin inhibits activity of mammalian target of rapamycin (mTOR), a master regulator of translational pathways in AML cells. Inhibiting the mTOR leads to a rapid killing of AML cells. Using these nanoconjugates we managed to successfully deliver rapamycin into the AML cells reaching attenuation of the mTOR activity. Concentration of rapamycin required to reach such an effect is at least 50 times lower compared to the one of free rapamycin required to achieve similar effect.ConclusionWe therefore concluded that our technology is of potential use for highly specific targeting of AML cells for the purpose of diagnosis and possibly therapy.2 The nanoconjugates can be used to specifically identify malignant blood cells thus allowing rapid AML diagnosis.ReferencesGoncalves Silva I, Yasinska IM, et al. E Bio Medicine 2017;22:44–57.Yasinska IM, et al. Nanoscale 2018 (in press).