(636e) ssDNA Nanotubes for Targeted Delivery of Doxorubicin to Triple Negative Breast Cancer Cells

With its lack of commonly targeted receptors, triple negative breast cancer (TNBC) is notoriously aggressive and difficult to treat. To address this problem, self-assembling single stranded DNA (ssDNA)-amphiphile nanotubes were used as a targeted delivery vehicle for doxorubicin (DOX) to TNBC cells. The ssDNA-amphiphiles were synthesized from a 10 nucleotide sequence attached to a dialkyl C₁₆ tail via a C₁₂ alkyl spacer, and have been previously shown to self-assemble into spherical micelles and nanotubes. The efficacy of these two different geometries was explored, with the nanotube geometry proving advantageous as it demonstrated increased internalization of the ssDNA-amphiphiles. The ssDNA nanotubes were shown to internalize into four different TNBC cell lines, SUM159, MDA-MB-231, MDA-MB-468, and BT549, and the mechanism of cell internalization was explored for all cancer cells. Interestingly, the nanotubes showed minimal internalization in healthy Hs578Bst breast cells, suggesting an inherent targeting ability in the absence of a specific targeting ligand. Due to DOX’s ability to intercalate into DNA, our ssDNA nanotubes were used to deliver DOX to the TNBC cells. Compared to free DOX, DOX-intercalated tubes proved equally cytotoxic to TNBC cells. Thus, these ssDNA nanotubes are a promising delivery vehicle that could be used for targeted delivery of therapeutics to TNBC cells.