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

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-12-12 eCollection Date: 2025-01-09 DOI:10.1021/acsmedchemlett.4c00480

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

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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.

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.