Small Peptide Ligands for Targeting EGFR in Triple Negative Breast Cancer Cells

Scientific Reports
Hanieh Hossein-Nejad-ArianiKamaljit Kaur

Abstract

The efficacy of chemotherapy for cancer treatment can be increased by targeted drug delivery to the cancer cells. This is particularly important for triple negative breast cancer (TNBC) for which chemotherapy is a major form of treatment. Here we designed and screened a library of 30 peptides starting with a previously reported epidermal growth factor receptor (EGFR) targeting peptide GE11 (YHWYGYTPQNVI). A direct peptide array-whole cell binding assay, where the peptides are conjugated to a cellulose membrane, was used to identify four peptides with enhanced binding to TNBC cells. Next, the four peptides were synthesized as FITC-labelled soluble peptides to study their direct uptake by TNBC cells using flow cytometry. The results showed that peptide analogue 22 had several fold higher uptake by the TNBC cells compared to the lead peptide GE11. The specific uptake of the peptide analogue 22 was confirmed by competition experiment using pure EGF protein. Further, peptide 22 showed dose dependent uptake by the TNBC MDA-MB-231 cells (105) with uptake saturating at around 2 μM peptide concentration. Thus, peptide 22 is a promising EGFR specific TNBC cell binding peptide that can be conjugated directly to a chemotherapeutic drug or ...Continue Reading

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Apr 2, 2020·International Journal of Molecular Sciences·Denis V VoroninDaniil N Bratashov
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Methods Mentioned

BETA
phage display
xenografts
antisense oligonucleotide
flow cytometry
peptide array
FACS
Fluorescence-activated cell-sorting

Software Mentioned

AutoSpot
Bio
ResPep SL
fold
Swiss
image lab
Pdb Viewer
PEP
Intavis

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