Arginine-rich ionic complementary peptides as potential drug carriers: Impact of peptide sequence on size, shape and cell specificity.

Ionic complementary peptides have shown potential in delivering hydrophobic anticancer drugs. In this study, a series of four ionic complementary peptides, EAR16-II, EAR8-II, EAR8-IIa and ELR8-IIa, is derived from the most studied ionic complementary peptide EAK16-II. The purpose is to investigate the impact of peptide sequence on nanostructure formation, delivery efficacy and cell specificity of the peptide-drug complex. We show that the peptide length has a pronounced impact on the morphology of peptide complex with the anticancer drug ellipticine (EPT), and the amino acid arrangement affects the complex size. Cytotoxicity studies show that the complexes are effective at inhibiting the growth of A549 lung cancer cells and EAR16-II-EPT is the most effective. Interestingly, the complexes formulated with EAR16-II and EAR8-II become less active against MCF-7 breast cancer cells, but more hemolytic than the other two complexes. This work provides essential information to optimize self-assembling peptide-based drug delivery for cancer therapy.

An amphipathic lytic peptide for enhanced and selective delivery of ellipticine.

Cationic lytic peptides (CLPs) have shown promise in treating bacterial infection and cancer via selective disruption of bacterial or cancer cell membranes. In this work, we used a CLP, C6, as a nanocarrier for a hydrophobic anticancer agent, ellipticine (EPT). The size of the resulting C6-EPT complex was ∼190 nm. The in vitro studies using A549 lung cancer cells showed an enhanced anticancer activity of the C6-EPT complex compared to that of C6 or the EPT control. This enhancement was found to correlate with the membrane disruption induced by C6, which facilitated the entry of EPT into cells. More importantly, the C6-EPT complex showed a higher selectivity than that of C6 towards cancer cells upon comparison of their cytotoxicities against A549 cells and NIH-3T3 fibroblast cells. The enhanced therapeutic activity was also found in in vivo studies using an A549 tumor-bearing BALB/c nude mice model. This study provides a new CLP strategy for the development of multifunctional drug delivery systems.