Aptameric GT oligomers need to be complexed to ethoxylated polyethylenimine as pre-paired duplexes to efficiently exert their cytotoxic activity in human lymphoblastic cancer cells

The aptameric oligonucleotides GT were found to exert a selective, specific and dose-dependent cell growth inhibition effect on a varietyof human cancer cells by recognising specific nuclear proteins and among these in particular an isoform of the eukaryotic elongation factor1A1 (EEF1A1). The potential development of these aptameric oligomers needs that they retain serum and intracellular stabilities. Polycationsare safe non-viral carriers of the nucleic acids.We demonstrated that a weakly basic polycation, the ethoxylated polyethylenimine (EPEI), canefficiently deliver cytotoxic GT oligomers when they were complexed as partial pre-paired duplex. In this way, nuclease-resistance of theoligomer was markedly improved and the administration of the duplex complexed with EPEI to lymphoblastic cancer cells caused a specificcytotoxic effect at concentrations lower than that of naked GT. However, the cytotoxic activity of the oligomer-EPEI complex resulted strictlyrelated to the GC content and Tm of the duplex region. The single-stranded GT and the duplex with high GC content and Tm, althoughcomplexed with EPEI failed to exert cytotoxicity. Overall results indicated that aptameric oligomers complexed with polycations can beefficiently delivered into the cells and display the desired biological effect designing a balanced partial duplex whose stability can allowoligomer release from the polycation under the physiological cellular conditions.