title: A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells.
abstract: Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Ki Jung
authors.initials: KJ
authors.lastname: Lim
authors.forename: Bong Hyun
authors.initials: BH
authors.lastname: Sung
authors.forename: Ju Ri
authors.initials: JR
authors.lastname: Shin
authors.forename: Young Woong
authors.initials: YW
authors.lastname: Lee
authors.forename: Da Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Kyung Seok
authors.initials: KS
authors.lastname: Yang
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D045325:HCT116 Cells; D006367:HeLa Cells; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D018613:Microscopy, Confocal; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D057127:Single-Chain Antibodies