Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

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

Authors Scherzinger-Laude K, Schönherr C, Lewrick F, Süss R, Francese G, Rössler J

Received 14 February 2013

Accepted for publication 22 March 2013

Published 20 June 2013 Volume 2013:8(1) Pages 2197—2211


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Readers of this article also read:

Monitoring cancer stem cells: insights into clinical oncology

Lin SC, Xu YC, Gan ZH, Han K, Hu HY, Yao Y, Huang MZ, Min DL

OncoTargets and Therapy 2016, 9:731-740

Published Date: 11 February 2016

BRAF mutation as a biomarker in colorectal cancer

Varghese AM, Saltz LB

Advances in Genomics and Genetics 2015, 5:347-353

Published Date: 15 October 2015

Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials

Van Heertum RL, Scarimbolo R, Ford R, Berdougo E, O’Neal M

Drug Design, Development and Therapy 2015, 9:5215-5223

Published Date: 11 September 2015

Skull base metastasis from papillary thyroid carcinoma: a report of three cases

Tunio MA, Al Asiri M, Al-Qahtani KH, Aldandan S, Riaz K, Bayoumi Y

International Medical Case Reports Journal 2015, 8:127-131

Published Date: 25 June 2015

Tracking the 2015 Gastrointestinal Cancers Symposium: bridging cancer biology to clinical gastrointestinal oncology

Aprile G, Leone F, Giampieri R, Casagrande M, Marino D, Faloppi L, Cascinu S, Fasola G, Scartozzi M

OncoTargets and Therapy 2015, 8:1149-1156

Published Date: 22 May 2015

Brachytherapy in the treatment of cervical cancer: a review

Banerjee R, Kamrava M

International Journal of Women's Health 2014, 6:555-564

Published Date: 28 May 2014

Application of liposomal technologies for delivery of platinum analogs in oncology

Liu D, He C, Wang AZ, Lin W

International Journal of Nanomedicine 2013, 8:3309-3319

Published Date: 26 August 2013

Multidisciplinary care in pediatric oncology

Cantrell MA, Ruble K

Journal of Multidisciplinary Healthcare 2011, 4:171-181

Published Date: 30 May 2011