title: Self/co-assembling peptide, EAR8-II, as a potential carrier for a hydrophobic anticancer drug pirarubicin (THP)--characterization and in-vitro delivery.
abstract: A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit advantages from two previously introduced peptides, AAP8 and EAK16-II, in their self/co-assembly. This peptide is short, simple, and inexpensive to synthesize, while possessing a low critical assembly concentration (CAC). The choice of alanine (A) residues in the peptide sequence provides moderate hydrophobic interactions, causing a minimal degree of aggregation, compared with other more hydrophobic residues. EAR8-II is an ionic-complementary peptide, similar to EAK16-II, can self/co-assemble with hydrophobic compounds such as THP, and forms a stable fibular nanostructure in aqueous solution. Physiochemical properties and cellular activities of the EAR8-II and THP complexes were evaluated and show dependency on the peptide-to-drug ratio. The complex at the peptide-to-drug mass ratio of 5:1 provides a stable solution, uniform nanostructure, and highly effective anticancer activity against various cancer cell lines. This work forms the basis for detailed studies on EAR8-II and THP formulations in vitro and in vivo, for future development of peptide-based delivery systems for hydrophobic anticancer drugs.
authors.affiliation: Department of Chemical Engineering and Waterloo Institute of Nanotechnology, University of Waterloo, Waterloo, ON N2L 3G1, Canada. p4chen@uwaterloo.ca.
authors.forename: Parisa
authors.initials: P
authors.lastname: Sadatmousavi
authors.forename: P
authors.initials: P
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D010455:Peptides; C000593724:acetyl-alanyl-glutamyl-alanyl-glutamyl-alanyl-arginyl-alanyl-argininamide; D004317:Doxorubicin; C027260:pirarubicin