CXCR4/CXCL12 axis plays a multifaceted role in cancer metastases, hematopoietic stem cell mobilization and chemosensitization. To design a new class of CXCR4 antagonists a rational design approach was taken based on the ligand structure. Four CXCL12 based- cyclopeptide CXCR4 inhibitors were discovered and shown to dramatically inhibit lung metastases development in ???in vivo??? models. Two novel anti CXCR4 cyclopeptides (Peptide L and R) were coupled to liposomes in order to improve the in vivo biodistribution of the peptides and to develop a new delivery system to target cancer cells overexpressing CXCR4. Preliminary evidences showed that Peptide R and S, conjugated to liposome, inhibit the migration of human renal cancer cells, RXF393, CXCR4 expressing, toward the specific ligand, CXCL12 more efficiently than AMD3100, the FDA-approved CXCR4 inhibitor. Moreover, a decrease in lung metastases was detected in C57Bl mice inoculated with B16-CXCR4 cells and treated twice a week intravenously with the Peptide R-conjugated liposome.

New CXCR4 inhibitors coupled with liposomes inhibit lung metastases development / Salzano, Giuseppina; L., Portella; A., Barbieri; P., Amodeo; Vitale, R. M.; S., De Luca; C., Arra; S., Scala; DE ROSA, Giuseppe. - (2012), pp. 0-0. (Intervento presentato al convegno 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. tenutosi a Istanbul (Turchia) nel 19-22 marzo 2012).

New CXCR4 inhibitors coupled with liposomes inhibit lung metastases development.

SALZANO, GIUSEPPINA;DE ROSA, GIUSEPPE
2012

Abstract

CXCR4/CXCL12 axis plays a multifaceted role in cancer metastases, hematopoietic stem cell mobilization and chemosensitization. To design a new class of CXCR4 antagonists a rational design approach was taken based on the ligand structure. Four CXCL12 based- cyclopeptide CXCR4 inhibitors were discovered and shown to dramatically inhibit lung metastases development in ???in vivo??? models. Two novel anti CXCR4 cyclopeptides (Peptide L and R) were coupled to liposomes in order to improve the in vivo biodistribution of the peptides and to develop a new delivery system to target cancer cells overexpressing CXCR4. Preliminary evidences showed that Peptide R and S, conjugated to liposome, inhibit the migration of human renal cancer cells, RXF393, CXCR4 expressing, toward the specific ligand, CXCL12 more efficiently than AMD3100, the FDA-approved CXCR4 inhibitor. Moreover, a decrease in lung metastases was detected in C57Bl mice inoculated with B16-CXCR4 cells and treated twice a week intravenously with the Peptide R-conjugated liposome.
2012
New CXCR4 inhibitors coupled with liposomes inhibit lung metastases development / Salzano, Giuseppina; L., Portella; A., Barbieri; P., Amodeo; Vitale, R. M.; S., De Luca; C., Arra; S., Scala; DE ROSA, Giuseppe. - (2012), pp. 0-0. (Intervento presentato al convegno 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. tenutosi a Istanbul (Turchia) nel 19-22 marzo 2012).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/510565
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