title: Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.
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 was 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.
  
  
  BACKGROUND
  GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles.
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Bernal
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: LaRiviere
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Nassir
authors.initials: N
authors.lastname: Mansour
authors.affiliation: Department of Pathology, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pytel
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Kirk E
authors.initials: KE
authors.lastname: Cahill
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Voce
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Kang
authors.affiliation: Biotarget Inc. and LNK Chemsolutions LLC, Lincoln, Nebraska, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Spretz
authors.affiliation: Material Science Division, Argonne National Laboratory, Argonne, Illinois, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welp
authors.affiliation: Biotarget Inc. and LNK Chemsolutions LLC, Lincoln, Nebraska, USA.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Noriega
authors.affiliation: Biotarget Inc. and LNK Chemsolutions LLC, Lincoln, Nebraska, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Nunez
authors.affiliation: Biotarget Inc. and LNK Chemsolutions LLC, Lincoln, Nebraska, USA.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Larsen
authors.affiliation: Department of Radiation and Cellular Oncology, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Bakhtiar
authors.initials: B
authors.lastname: Yamini
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D045744:Cell Line, Tumor; D018481:Convection; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000737:chemistry; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D011859:Radiography; D051381:Rats; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Convection; Glioma; MRI; Nanoparticle
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