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

doi:10.1016/j.apsb.2023.03.024

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

Acta Pharm Sin B. 2023 Sep;13(9):3849-3861. doi: 10.1016/j.apsb.2023.03.024. Epub 2023 Mar 31.

Authors

Chen Li^{1

2}, Jiayan Lang^{1

2}, Yazhou Wang³, Zhaoxia Cheng^{1

4}, Mali Zu^{1

2}, Fenfen Li^{1

5}, Jingyi Sun^{1

2}, Yating Deng^{1

2}, Tianjiao Ji^{1

2}, Guangjun Nie^{1

2}, Ying Zhao^{1

2}

Affiliations

¹ CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
² Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Pancreas Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
⁴ Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
⁵ School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Abstract

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.

Keywords: CXCR4; Docetaxel; Drug delivery; Drug formulation; Peptide–drug conjugates; Triple-negative breast cancer; Tumor metastasis.