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Breast cancer remains a leading cause of morbidity and mortality among women worldwide, emphasizing the urgent need for enhanced diagnostic and therapeutic approaches. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has emerged as a notable target due to its markedly elevated expression in breast tumors, suggesting the viability of LRG1 as a theranostic target. In our study, we employed phage display technology to identify a peptide, termed ET, that binds to LRG1 with a dissociation constant of 48.4 μM. After modified with fluorescent cyanine dye, the ET peptide showcased effective tumor-targeting imaging across three different primary breast tumor models and a metastatic breast tumor model. We also undertook a comprehensive safety evaluation, which verified the good biosafety credentials of ET peptide. In summary, the ET peptide identified in this study shows effective LRG1-targeting ability both in vitro and in vivo, thus exhibiting immense potential for clinical translation.


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Identification of LRG1 targeting peptide and its application in targeted imaging for breast cancer

Show Author's information Mengdie Chen1,2,§Anying Zhu1,3,§Furong Zhu1Ziwen Lei1Tao Huang4Shengnan Du1Dongdong Wang5Xiaoyu Zhang5( )Huan Min1,2( )Yingqiu Qi1,2( )Guangjun Nie6
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450008, China
Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Department of Breast Disease, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450003, China
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, 11 Beiyitiao, Zhongguancun, Beijing 100190, China

§ Mengdie Chen and Anying Zhu contributed equally to this work.

Abstract

Breast cancer remains a leading cause of morbidity and mortality among women worldwide, emphasizing the urgent need for enhanced diagnostic and therapeutic approaches. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has emerged as a notable target due to its markedly elevated expression in breast tumors, suggesting the viability of LRG1 as a theranostic target. In our study, we employed phage display technology to identify a peptide, termed ET, that binds to LRG1 with a dissociation constant of 48.4 μM. After modified with fluorescent cyanine dye, the ET peptide showcased effective tumor-targeting imaging across three different primary breast tumor models and a metastatic breast tumor model. We also undertook a comprehensive safety evaluation, which verified the good biosafety credentials of ET peptide. In summary, the ET peptide identified in this study shows effective LRG1-targeting ability both in vitro and in vivo, thus exhibiting immense potential for clinical translation.

Keywords: breast cancer, tumor targeting, peptide, phage display, leucine-rich-alpha-2-glycoprotein 1 (LRG1)

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Publication history
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Acknowledgements

Publication history

Received: 25 August 2023
Revised: 13 October 2023
Accepted: 13 October 2023
Published: 17 November 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

The authors thank Prof. Bing Jiang (Zhengzhou University) for assistance with the fluorescence imaging. The authors also thank the center of Advanced Analysis & Gene Sequencing, Zhengzhou University for technical assistance. This work was supported by grants from the National Natural Science Foundation of China (Nos. 32000998 and 32201240). The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology (No. 2022HYTP046) and the China Postdoctoral Science Foundation (No. 2021TQ0298), and Science and Technology Development Project of Henan Province (Nos. 222102310525, 232102310351), and National College Students’ innovation and entrepreneurship training program (No. 202310459197).

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