Convection enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma

Authors

Giovanna M. Bernal, University of Chicago
Michael J. LaRiviere, University of Chicago
Nassir Mansour, University of Chicago
Peter Pytel, University of Chicago
Kirk E. Cahill, University of Chicago
David J. Voce, University of Chicago
Shijun Kang, University of Chicago
Rubin Spretz, Biotarget Inc. and LNK Chemsolutions LLC
Ulrich Welp, Argonne National Laboratory
Sandra E. Noriega, Biotarget Inc. and LNK Chemsolutions LLC
Luis Nunez, Biotarget Inc. and LNK Chemsolutions LLC
Gustavo F. Larsen, University of Nebraska - LincolnFollow
Ralph R. Weichselbaum, University of Chicago
Bakhtiar Yamini, University of Chicago

Date of this Version

2014

Document Type

Article

Citation

Nanomedicine. 2014 January ; 10(1): .

Comments

Copyright © 2014 Elsevier Inc.

Abstract

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells demonstrated. Convection enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma.