A Conjugate of an EGFR-Binding Peptide and Doxorubicin Shows Selective Toxicity to Triple-Negative Breast Cancer Cells

Authors

Phi-Phung Than, Chapman University
Shih-Jing Yao, Chapman University
Emad Althagafi, Chapman University
Kamaljit Kaur, Chapman UniversityFollow

Document Type

Article

Publication Date

12-12-2024

Abstract

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

Comments

This letter was originally published in ACS Medicinal Chemistry Letters, volume 16, issue 1, in 2024. https://doi.org/10.1021/acsmedchemlett.4c00480

Recommended Citation

Than, P.-P.; Yao, S.-J.; Althagafi, E.; Kaur, K. A conjugate of an EGFR-binding peptide and doxorubicin shows selective toxicity to triple-negative breast cancer cells. ACS Med. Chem. Lett. 2025, 16, 109−115. https://doi.org/10.1021/acsmedchemlett.4c00480

Copyright

American Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.