A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells
Open Access
- 11 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e66084
- https://doi.org/10.1371/journal.pone.0066084
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.This publication has 47 references indexed in Scilit:
- Role of Helicity on the Anticancer Mechanism of Action of Cationic-Helical PeptidesInternational Journal of Molecular Sciences, 2012
- Clathrin-independent endocytosis: mechanisms and functionCurrent Opinion in Cell Biology, 2011
- Mechanisms of Cellular Uptake of Cell-Penetrating PeptidesJournal of Biophysics, 2011
- Quantum dots labeling using octa-arginine peptides for imaging of adipose tissue-derived stem cellsBiomaterials, 2010
- Building Cell Selectivity into CPP-Mediated StrategiesPharmaceuticals, 2010
- Cell-Penetrating Peptides—Mechanisms of Cellular Uptake and Generation of Delivery SystemsPharmaceuticals, 2010
- Twenty years of cell‐penetrating peptides: from molecular mechanisms to therapeuticsBritish Journal of Pharmacology, 2009
- A New Potent Secondary Amphipathic Cell–penetrating Peptide for siRNA Delivery Into Mammalian CellsMolecular Therapy, 2009
- Positively Charged DNA-Binding Proteins Cause Apparent Cell Membrane TranslocationBiochemical and Biophysical Research Communications, 2002
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976