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

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.