Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer

Changliang Liu; Hongyang Duan; Zijian Zhao; Wenzhe Li; Lilusi Ma; Xiaocui Fang; Chen Wang; Yanlian Yang

doi:10.1039/c8ra08526a

Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer

RSC Adv. 2018 Nov 30;8(70):39948-39956. doi: 10.1039/c8ra08526a. eCollection 2018 Nov 28.

Authors

Changliang Liu¹, Hongyang Duan^{1

2}, Zijian Zhao¹, Wenzhe Li^{1

2}, Lilusi Ma¹, Xiaocui Fang¹, Chen Wang¹, Yanlian Yang¹

Affiliations

¹ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology Beijing 100190 P. R. China fangxc@nanoctr.cn wangch@nanoctr.cn yangyl@nanoctr.cn +86-10-82545561 +86-10-82545559.
² Academy for Advanced Interdisciplinary Studies, Peking University Beijing 100871 China.

Abstract

The metastasis of breast cancer is one of the main factors resulting in the high fatality of patients. Although many antagonists have been developed to inhibit the metastasis of breast cancer, their practical application has been limited because of the poor solubility of many chemotherapeutic drugs in the physiological environment. Herein, a complex of E5 peptide antagonist and acetylated PAMAM G5 (P_AC80) has been constructed to enhance the solubility of the peptide antagonist. The E5 peptide antagonist has been designed and it was confirmed that it could specifically bind to CXCR4, which is a chemokine receptor involved in the metastasis of several types of cancers, in our previous work. The results demonstrated that P_AC80 could significantly increase the solubility of the E5 peptide in the physiological environment, as well as the affinity of the E5 peptide to CXCR4-positive cell lines, and the inhibitory effect of the E5 peptide for cell migration in vitro. Meanwhile, the passive lung metastasis model of breast cancer was established and the anti-tumor metastasis of the P_AC80-E5 complex was evaluated in vivo. The results show that the P_AC80-E5 complex demonstrated excellent inhibition for the tumor metastasis at an E5 dosage of 10 and 20 mg kg^-1. These effects indicate a feasible strategy to apply the P_AC80-peptide complex in cancer therapies to improve the solubility and bioavailability.