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

Area of Science:

• Oncology
• Biotechnology
• Molecular Biology

Background:

• Chemotherapy efficacy for cancer treatment can be improved through targeted drug delivery.
• Triple-negative breast cancer (TNBC) is a major subtype where chemotherapy is a primary treatment modality.
• Targeting specific cell receptors, like the epidermal growth factor receptor (EGFR), is a key strategy for enhancing drug delivery.

Purpose of the Study:

• To design and screen novel peptides for enhanced binding and uptake by TNBC cells.
• To identify a peptide that specifically targets EGFR on TNBC cells for improved drug delivery.
• To evaluate the potential of a new peptide for targeted chemotherapy in TNBC.

Main Methods:

• Screening of 30 designed peptides using a direct peptide array-whole cell binding assay.
• Synthesis of four high-binding peptides as FITC-labelled soluble peptides.
• Quantification of TNBC cell uptake using flow cytometry and competition assays with EGF protein.

Main Results:

• Identified four peptides with enhanced binding to TNBC cells compared to the lead peptide GE11.
• Peptide analogue 22 demonstrated several-fold higher cellular uptake in TNBC cells than GE11.
• Specific uptake of peptide 22 was confirmed by competition with EGF, and it showed dose-dependent uptake saturating at 2 μM.

Conclusions:

• Peptide analogue 22 is a potent EGFR-specific peptide with superior binding and uptake characteristics for TNBC cells.
• Peptide 22 holds significant promise for direct conjugation to chemotherapeutics or nanoparticles for targeted TNBC drug delivery.
• This targeted approach using peptide 22 could enhance the efficacy of chemotherapy in TNBC treatment.