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

Nanomedicine. 2014 Jan;10(1):149-57. doi: 10.1016/j.nano.2013.07.003. Epub 2013 Jul 24.

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.

From the clinical editor: 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.

Keywords: Convection; Glioma; MRI; Nanoparticle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Convection
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / chemistry
  • Drug Delivery Systems*
  • Ferric Compounds / chemistry
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Polymers / chemistry
  • Polymers / therapeutic use
  • Radiography
  • Rats
  • Temozolomide
  • Xenograft Model Antitumor Assays

Substances

  • Ferric Compounds
  • Polymers
  • ferric oxide
  • Dacarbazine
  • Temozolomide