A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells

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 antican...

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Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e66084-e66084
Main Authors: Lim, Ki Jung, Sung, Bong Hyun, Shin, Ju Ri, Lee, Young Woong, Kim, Da Jung, Yang, Kyung Seok, Kim, Sun Chang
Format: Article
Language:English
Subjects:
Amino acids
Apoptosis
Apoptosis - physiology
Biology
Blotting, Western
Cancer
Cancer cells
Cancer therapies
Cancer treatment
Cell Proliferation
Cell-Penetrating Peptides - chemistry
Cell-Penetrating Peptides - metabolism
Cytotoxicity
Derivatives
Design
Drug carriers
Drug delivery
Drug delivery systems
Endocytosis - physiology
Fibroblasts
Gangliosides
HCT116 Cells
HeLa Cells
Hemolysis - physiology
Humans
K-Ras protein
Medicine
Metastasis
Microscopy
Microscopy, Confocal
Peptides
Proteins
Quantum dots
Science
Single-Chain Antibodies - chemistry
Single-Chain Antibodies - metabolism
Toxicity
Translocation
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066084