A special class of self-assembling
peptides has been found to be capable of stabilizing the hydrophobic
anticancer agent ellipticine in aqueous
solution. Here we study the effect of
peptide sequence on the complex formation and its anticancer activity in vitro. Three
peptides, EAK16-II, EAK16-IV and EFK16-II, were selected to have either a different charge distribution (EAK16-II vs. EAK16-IV) or a varying hydrophobicity (EAK16-II vs. EFK16-II). Results on their complexation with
ellipticine revealed that EAK16-II and EAK16-IV were able to stabilize protonated
ellipticine or
ellipticine microcrystals depending on the
peptide concentration; EFK16-II could stabilize neutral
ellipticine molecules and
ellipticine microcrystals. These different molecular states of
ellipticine were expected to affect
ellipticine delivery. The anticancer activity of these complexes was tested against two
cancer cell lines: A549 and MCF-7, and related to the cell viability. The viability results showed that the complexes with protonated
ellipticine were effective in eradicating both
cancer cells (viability <0.05), but their dilutions in water were not stable, leading to a fast decrease in their toxicity. In contrast, the complexes formulated with EFK16-II were relatively stable upon dilution, but their original toxicity was relatively low compared to that with protonated
ellipticine. Overall, the charge distribution of the
peptides seemed not to affect the complex formation and its therapeutic efficacy in vitro; however, the increase in hydrophobicity of the
peptides significantly altered the state of stabilized
ellipticine and increased the stability of the complexes. This work provides essential information for
peptide sequence design in the development of self-assembling
peptide-based delivery of hydrophobic anticancer drugs.