Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)

Karine Scherzinger-Laude,1 Carina Schönherr,2,3 Felicitas Lewrick,3 Regine Süss,3 Giancarlo Francese,2,* Jochen Rössler1,* 1Clinic IV, Pediatric Hematology and Oncology, Center of Pediatrics and Adolescent Medicine, University Medical Hospital Freiburg, Germany; 2Departmen...

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Autores principales:	Scherzinger-Laude K, Sch&ouml;nherr C, Lewrick F, S&uuml;ss R, Francese G, R&ouml;ssler J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a1a61f603b244a749d3eb77293d311b3
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spelling	oai:doaj.org-article:a1a61f603b244a749d3eb77293d311b32021-12-02T02:11:17ZTreatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)1176-91141178-2013https://doaj.org/article/a1a61f603b244a749d3eb77293d311b32013-06-01T00:00:00Zhttp://www.dovepress.com/treatment-of-neuroblastoma-and-rhabdomyosarcoma-using-rgd-modified-lip-a13421https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Karine Scherzinger-Laude,1 Carina Schönherr,2,3 Felicitas Lewrick,3 Regine Süss,3 Giancarlo Francese,2,* Jochen Rössler1,* 1Clinic IV, Pediatric Hematology and Oncology, Center of Pediatrics and Adolescent Medicine, University Medical Hospital Freiburg, Germany; 2Department of Technical Research and Development, Novartis Pharma AG, Basel, Switzerland; 3Department of Pharmaceutical Technology, Albert-Ludwigs University, Freiburg, Germany *Both authors contributed equally to this work as senior scientists Background: Patupilone (EPO906) is a microtubule stabilizer with a potent antitumor effect. Integrin αVß3-binding (RGD) liposomes were loaded with EPO906, and their antitumor efficacy was evaluated in two pediatric tumor models, ie, neuroblastoma and rhabdomyosarcoma. Methods: Integrin αVß3 gene expression, RGD-liposome cellular association, and the effect of EPO906 and liposomal formulations of EPO906 on cell viability were assessed in vitro in human umbilical vein endothelial cells (HUVEC), in the RH-30 rhabdomyosarcoma cell line, and in the Kelly neuroblastoma cell line. In vivo, mice bearing neuroblastoma or rhabdomyosarcoma tumors were treated with EPO906, EPO906-liposomes, or EPO906-RGD-liposomes. Tumor growth, cumulative survival, and toxicity were monitored. Results: Integrin αVß3 was highly expressed in HUVEC and RH-30, but not in Kelly cells. Accordingly, RGD-liposomes were highly associated with HUVEC and RH-30 cells in vitro, but not with the Kelly cells. EPO906 and its liposomal formulations inhibited HUVEC, RH-30, and Kelly cell viability to the same extent. In vivo, EPO906 1.5 mg/kg and liposomal EPO906 potently inhibited tumor growth in both xenograft models without triggering major toxicity. At this dose, liposomal EPO906 did not enhance the antitumor effect of EPO906 in neuroblastoma, but tended to have an increased antitumor effect in rhabdomyosarcoma. Using a lower dose of EPO906-RGD-liposomes significantly enhanced cumulative survival in rhabdomyosarcoma compared with EPO906 alone. Conclusion: EPO906 shows a strong antitumor effect in neuroblastoma and rhabdomyosarcoma, without triggering major side effects. Its liposomal encapsulation does not alter its activity, and enhances cumulative survival when EPO906-RGD-liposomes are used at low dose in rhabdomyosarcoma. Keywords: patupilone, liposomes, integrin targeting, pediatric cancerScherzinger-Laude KSch&ouml;nherr CLewrick FS&uuml;ss RFrancese GR&ouml;ssler JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2197-2211 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Scherzinger-Laude K Sch&ouml;nherr C Lewrick F S&uuml;ss R Francese G R&ouml;ssler J Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
description	Karine Scherzinger-Laude,1 Carina Schönherr,2,3 Felicitas Lewrick,3 Regine Süss,3 Giancarlo Francese,2,* Jochen Rössler1,* 1Clinic IV, Pediatric Hematology and Oncology, Center of Pediatrics and Adolescent Medicine, University Medical Hospital Freiburg, Germany; 2Department of Technical Research and Development, Novartis Pharma AG, Basel, Switzerland; 3Department of Pharmaceutical Technology, Albert-Ludwigs University, Freiburg, Germany *Both authors contributed equally to this work as senior scientists Background: Patupilone (EPO906) is a microtubule stabilizer with a potent antitumor effect. Integrin αVß3-binding (RGD) liposomes were loaded with EPO906, and their antitumor efficacy was evaluated in two pediatric tumor models, ie, neuroblastoma and rhabdomyosarcoma. Methods: Integrin αVß3 gene expression, RGD-liposome cellular association, and the effect of EPO906 and liposomal formulations of EPO906 on cell viability were assessed in vitro in human umbilical vein endothelial cells (HUVEC), in the RH-30 rhabdomyosarcoma cell line, and in the Kelly neuroblastoma cell line. In vivo, mice bearing neuroblastoma or rhabdomyosarcoma tumors were treated with EPO906, EPO906-liposomes, or EPO906-RGD-liposomes. Tumor growth, cumulative survival, and toxicity were monitored. Results: Integrin αVß3 was highly expressed in HUVEC and RH-30, but not in Kelly cells. Accordingly, RGD-liposomes were highly associated with HUVEC and RH-30 cells in vitro, but not with the Kelly cells. EPO906 and its liposomal formulations inhibited HUVEC, RH-30, and Kelly cell viability to the same extent. In vivo, EPO906 1.5 mg/kg and liposomal EPO906 potently inhibited tumor growth in both xenograft models without triggering major toxicity. At this dose, liposomal EPO906 did not enhance the antitumor effect of EPO906 in neuroblastoma, but tended to have an increased antitumor effect in rhabdomyosarcoma. Using a lower dose of EPO906-RGD-liposomes significantly enhanced cumulative survival in rhabdomyosarcoma compared with EPO906 alone. Conclusion: EPO906 shows a strong antitumor effect in neuroblastoma and rhabdomyosarcoma, without triggering major side effects. Its liposomal encapsulation does not alter its activity, and enhances cumulative survival when EPO906-RGD-liposomes are used at low dose in rhabdomyosarcoma. Keywords: patupilone, liposomes, integrin targeting, pediatric cancer
format	article
author	Scherzinger-Laude K Sch&ouml;nherr C Lewrick F S&uuml;ss R Francese G R&ouml;ssler J
author_facet	Scherzinger-Laude K Sch&ouml;nherr C Lewrick F S&uuml;ss R Francese G R&ouml;ssler J
author_sort	Scherzinger-Laude K
title	Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
title_short	Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
title_full	Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
title_fullStr	Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
title_full_unstemmed	Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
title_sort	treatment of neuroblastoma and rhabdomyosarcoma using rgd-modified liposomal formulations of patupilone (epo906)
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/a1a61f603b244a749d3eb77293d311b3
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Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)

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