A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells

University of Pittsburgh, United States of America
PLoS ONE (Impact Factor: 3.23). 11/2013; 8(6):e66084. DOI: 10.1371/journal.pone.0066084
Source: PubMed


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.

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    • "As examples, cathelicidin is been a potential therapeutic peptide for gastrointestinal inflammation and cancer [47] and a 15-mer peptide from the follicle-stimulating hormone support the anti-tumor activity of paclitaxel nanoparticles against ovarian cancers [48]. The cancer-specific peptide BR2 penetrates cancer cells, and has been shown to mediate the delivery of a scFv into cancer cells [49]. The therapeutic capabilities of peptides have been demonstrated by a report of a peptide which is able to induce apoptosis in SKOV3 cells by down-regulating Bcl-2 [50]. "
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