Nanocarriers and nonviral methods for delivering antiangiogenic factors for glioblastoma therapy: the story so far

Abstract

Angiogenesis, the formation of new blood vessels, is an essential component of glioblastoma (GB) progression. The development of angiogenesis inhibitor therapy, including treatments targeting vascular endothelial growth factor (VEGF) in particular, raised new hopes for the treatment of GB, but no Phase III clinical trial to date has reported survival benefits relative to standard treatment. There are several possible reasons for this limited efficacy, including VEGF-independent angiogenesis, induction of tumor invasion, and inefficient antiangiogenic factor delivery to the tumor. Efforts have been made to overcome these limitations by identifying new angiogenesis inhibitors that target angiogenesis through different mechanisms of action without inducing tumor invasion, and through the development of viral and nonviral delivery methods to improve antiangiogenic activity. Herein, we describe the nonviral methods, including convection-enhanced delivery devices, implantable polymer devices, nanocarriers, and cellular vehicles, to deliver antiangiogenic factors. We focus on those evaluated in intracranial (orthotopic) animal models of GB, the most relevant models of this disease, as they reproduce the clinical scenario of tumor progression and therapy response encountered in GB patients.

Keywords:

• antiangiogenic factors
• delivery methods
• glioblastoma
• convection-enhanced delivery devices
• implantable polymer devices
• nanocarriers
• cellular vehicles

Acknowledgments

This work was supported by grants from the “Fondation de France”, “Ligue Contre le Cancer du Grand-Ouest, Comité Départemental du Maine-et-Loire”, “Association en Avant la Vie”, and the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), through the NanoFar Erasmus Mundus joint Doctoral program. We thank Professor Franck Boury (Team 17, GLIAD, CRCINA, INSERM 1232, Angers), Doctor Snow Stolnik, and Doctor Cynthia Bosquillon (School of Pharmacy, University of Nottingham, Nottingham, UK) for providing facilities. We also thank Alex Edelman and associates for correcting the manuscript.

Disclosure

The authors report no conflicts of interest in this work.