Self-assembly of CXCR4 antagonist peptide–docetaxel conjugates for breast tumor multi-organ metastasis inhibition

Chen Li; Jiayan Lang; Yazhou Wang; Zhaoxia Cheng; Mali Zu; Fenfen Li; Jingyi Sun; Yating Deng; Tianjiao Ji; Guangjun Nie; Ying Zhao

Acta Pharmaceutica Sinica B (Sep 2023)

Self-assembly of CXCR4 antagonist peptide–docetaxel conjugates for breast tumor multi-organ metastasis inhibition

Chen Li,
Jiayan Lang,
Yazhou Wang,
Zhaoxia Cheng,
Mali Zu,
Fenfen Li,
Jingyi Sun,
Yating Deng,
Tianjiao Ji,
Guangjun Nie,
Ying Zhao

Affiliations

Chen Li: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Jiayan Lang: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Yazhou Wang: Pancreas Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Zhaoxia Cheng: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
Mali Zu: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Fenfen Li: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Jingyi Sun: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Yating Deng: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Tianjiao Ji: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.
Guangjun Nie: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.
Ying Zhao: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authors.

Journal volume & issue: Vol. 13, no. 9
pp. 3849 – 3861

Abstract

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As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C–X–C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE–DTX) as an anti-metastasis agent to treat breast cancer. CTCE–DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE–DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide–drug conjugates with synergistic anti-tumor efficacy.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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