title: CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.
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.
authors.affiliation: Molecular Immunology and Immune regulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy. s.scala@istitutotumori.na.it s.scala@gmail.com.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ieranò
authors.affiliation: Molecular Immunology and Immune regulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy. s.scala@istitutotumori.na.it s.scala@gmail.com.
authors.forename: Luigi
authors.initials: L
authors.lastname: Portella
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy. gderosa@unina.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Lusa
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy. gderosa@unina.it and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, 360 Huntington Ave, Boston, MA, USA.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Salzano
authors.affiliation: Molecular Immunology and Immune regulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy. s.scala@istitutotumori.na.it s.scala@gmail.com.
authors.forename: Crescenzo
authors.initials: C
authors.lastname: D'Alterio
authors.affiliation: Molecular Immunology and Immune regulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy. s.scala@istitutotumori.na.it s.scala@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Buoncervello
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Macchia
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.affiliation: Animal Facility, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbieri
authors.affiliation: Animal Facility, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.affiliation: Department of Translational Medical Science and European Laboratory for the Investigation of Food Induced Disease (ELFID), University of Naples, Federico II, Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Barone
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gabriele
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via L. De Crecchio 7, 80138, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Animal Facility, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy. gderosa@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.affiliation: Molecular Immunology and Immune regulation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione "G. Pascale"-IRCCS, Italy. s.scala@istitutotumori.na.it s.scala@gmail.com.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D064593:Heterografts; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D008081:Liposomes; D010455:Peptides; D019718:Receptors, CXCR4; D004317:Doxorubicin