A Conjugate\nof an EGFR-Binding Peptide and Doxorubicin\nShows Selective Toxicity to Triple-Negative Breast Cancer Cells

Selective targeting of cancer cells via overexpressed\ncell-surface\nreceptors is a promising strategy to enhance chemotherapy efficacy\nand minimize off-target side effects. In this study, we designed peptide\n31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor\nreceptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide\n31 is internalized by TNBC cells through EGFR-mediated endocytosis\nand shares sequence and structural similarities with human EGF (hEGF),\na natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell\nmigration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin\n(Dox) retains selectivity for TNBC cells and exhibits significant\ntoxicity comparable to that of unconjugated Dox. Importantly, this\nconjugate shows no toxicity toward normal breast epithelial cells\nup to a high concentration (25 μM). Thus, peptide 31 serves\nas a versatile targeting ligand for developing novel conjugates with\nhigh selectivity for EGFR-positive cancers.