Lipophilic pro-oligonucleotides are rapidly and efficiently internalized in HeLa cells

Model t-Bu-SATE pro-dodecathymidines labeled with fluorescein and exhibiting various lipophilicities were evaluated for their uptake by cells in culture. Pro-oligonucleotides with appropriate lipophilicity were found to permeate across the HeLa cell membrane much more extensively than the control phosphorothioate oligo or than the hydrophilic prooligos. Fluorescence patterns of internalization were consistent with a diffusion mechanism resulting in the appearance of a uniform cytoplasmic distribution and nuclear accumulation, as confirmed by confocal microscopy.