CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

Caterina Ieranò, Luigi Portella, Sara Lusa, Giuseppina Salzano, Crescenzo D'Alterio, Maria Napolitano, Maria Buoncervello, Daniele Macchia, Massimo Spada, Antonio Barbieri, Antonio Luciano, Maria Vittoria Barone, Lucia Gabriele, Michele Caraglia, Claudio Arra, Giuseppe De Rosa, Stefania Scala

Research output: Contribution to journalArticlepeer-review

Abstract

The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.

Original languageEnglish
Pages (from-to)7562-7571
Number of pages10
JournalNanoscale
Volume8
Issue number14
DOIs
Publication statusPublished - Apr 14 2016

ASJC Scopus subject areas

  • Materials Science(all)

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