Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma

Jai Seo, JooChuan Ang, Lisa M. Mahakian, Sarah Tam, Brett Fite, Elizabeth S. Ingham, Janine Beyer, John Forsayeth, Krystof S. Bankiewicz, Ting Xu, Katherine W. Ferrara

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers. While the circulation half-life of the 3HM was similar to 110-nm PEGylated liposomes (t1/2 = 15.5 and 16.5 h, respectively), the 20-nm micelles greatly enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous injection. After accounting for tumor blood volume, the extravasated nanoparticles were quantified from the PET images, yielding ~ 0.77%ID/cm3 for the micelles and 0.45%ID/cm3 for the liposomes. For GBM lesions with a volume greater than 100 mm3, 3HM accumulation was enhanced both within the detectable tumor and in the surrounding brain parenchyma. Further, the nanoparticle accumulation was shown to extend to the margins of the GBM xenograft. In summary, 3HM provides an attractive nanovehicle for carrying treatment to GBM.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalJournal of Controlled Release
Volume220
DOIs
StatePublished - Dec 28 2015

    Fingerprint

Keywords

  • BBB
  • Blood brain barrier
  • Drug delivery
  • Glioblastoma
  • Liposome
  • Micelles
  • Nanoparticle
  • PET
  • PET/MR
  • Positron emission tomography

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Seo, J., Ang, J., Mahakian, L. M., Tam, S., Fite, B., Ingham, E. S., Beyer, J., Forsayeth, J., Bankiewicz, K. S., Xu, T., & Ferrara, K. W. (2015). Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma. Journal of Controlled Release, 220, 51-60. https://doi.org/10.1016/j.jconrel.2015.09.057