Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma

Eun Ji Chung, Yu Cheng, Ramin Morshed, Kathryn Nord, Yu Han, Michelle L. Wegscheid, Brenda Auffinger, Derek A. Wainwright, Maciej S. Lesniak, Matthew V. Tirrell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1h after administration, as confirmed via invivo and exvivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma.

Original languageEnglish (US)
Pages (from-to)1249-1256
Number of pages8
JournalBiomaterials
Volume35
Issue number4
DOIs
StatePublished - Jan 2014

Keywords

  • Brain
  • Diagnostic
  • Glioblastoma
  • Micelle
  • Self-assembly
  • Targeting

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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