دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Treatment of neuroblastoma and rhabdomyosarcoma using RGD-modified liposomal formulations of patupilone (EPO906)
المؤلفون: Scherzinger-Laude K, Schönherr C, Lewrick F, Süss R, Francese G, Rössler J
المصدر: International Journal of Nanomedicine, Vol 2013, Iss default, Pp 2197-2211 (2013)
بيانات النشر: Dove Medical Press, 2013.
سنة النشر: 2013
المجموعة: LCC:Medicine (General)
مصطلحات موضوعية: Medicine (General), R5-920
الوصف: 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
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1176-9114
1178-2013
Relation: http://www.dovepress.com/treatment-of-neuroblastoma-and-rhabdomyosarcoma-using-rgd-modified-lip-a13421; https://doaj.org/toc/1176-9114; https://doaj.org/toc/1178-2013
URL الوصول: https://doaj.org/article/a1a61f603b244a749d3eb77293d311b3
رقم الأكسشن: edsdoj.1a61f603b244a749d3eb77293d311b3
قاعدة البيانات: Directory of Open Access Journals