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A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy

Tumor-targeting peptide–drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting pepti...

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Detalles Bibliográficos
Autores principales: Liu, Shurong, Tian, Ye, Jiang, Sujun, Wang, Zihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003747/
https://www.ncbi.nlm.nih.gov/pubmed/36902021
http://dx.doi.org/10.3390/ijms24054590
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author Liu, Shurong
Tian, Ye
Jiang, Sujun
Wang, Zihua
author_facet Liu, Shurong
Tian, Ye
Jiang, Sujun
Wang, Zihua
author_sort Liu, Shurong
collection PubMed
description Tumor-targeting peptide–drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC(50) of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy.
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spelling pubmed-100037472023-03-11 A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy Liu, Shurong Tian, Ye Jiang, Sujun Wang, Zihua Int J Mol Sci Article Tumor-targeting peptide–drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC(50) of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy. MDPI 2023-02-27 /pmc/articles/PMC10003747/ /pubmed/36902021 http://dx.doi.org/10.3390/ijms24054590 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Shurong
Tian, Ye
Jiang, Sujun
Wang, Zihua
A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title_full A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title_fullStr A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title_full_unstemmed A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title_short A Novel Homodimer Peptide–Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy
title_sort novel homodimer peptide–drug conjugate improves the efficacy of her2-positive breast cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003747/
https://www.ncbi.nlm.nih.gov/pubmed/36902021
http://dx.doi.org/10.3390/ijms24054590
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