Song, S.J., Lee, S., Ryu, K.S., Choi, J.S. (2017) Amphiphilic peptide nanorods based on oligo-phenylalanine as a biocompatible drug carrier. Bioconjugate Chemistry. 28(9):2266-2276.
Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH3F8 (Arg-His3-Phe8), as a drug-delivery carrier. Arginine is an essential amino acid in typical cell-penetration peptides, and histidine induces endo- and lysosomal escape because of its proton sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for stable self-assembly and drug encapsulation. The self-assembled structure of RH3F8 showed nanorod-shaped morphology, positive surface charge, and retained formation in water for 35 days. RH3F8, labeled with Nile Red, showed high cellar uptake and accumulation in both cytoplasm and nucleus. The RH3F8 nanorods demonstrated negligible cytotoxicity, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and hemolysis assays. To confirm the efficiency of drug delivery, curcumin was encapsulated in the RH3F8 nanorod system (RH3F8-Cur). RH3F8-Cur showed high encapsulation efficiency (24.63%) under the conditions of 200 μM curcumin. The RH3F8-Cur retained nanoscale size and positive surface charge, similar to those of the empty RH3F8 nanorods. RH3F8-Cur displayed a robust anticancer effect in HeLa and A549 cells, and inhibited the proliferation of cancer cells in a zebrafish model. These results indicate that the RH3F8 nanorods may be a promising candidate for a safe and effective drug-delivery system.