Nanoparticle delivery of a peptide targeting EGFR signaling

J Control Release. 2012 Jan 30;157(2):279-86. doi: 10.1016/j.jconrel.2011.08.014. Epub 2011 Aug 17.


EGFR serves as an important therapeutic target because of its over-expression in many cancers. In this study, we investigated a peptide-based therapy aimed at blocking intracellular protein-protein interactions during EGFR signaling and evaluated a targetable lipid carrier system that can deliver peptides to intracellular targets in human cancer cells. EEEEpYFELV (EV), a nonapeptide mimicking the Y845 site of EGFR which is responsible for STAT5b phosphorylation, was designed to block EGFR downstream signaling. EV was loaded onto LPH nanoparticles that are comprised of a membrane/core structure including a surface-grafted polyethylene glycol (PEG) used to evade the reticuloendothelial system (RES) and anisamide (AA) for targeting the sigma receptor over-expressed in H460 human lung cancer cells. EV formulated with PEGylated and targeted LPH (LPH-PEG-AA) was taken up by the tumor cells and trafficked to the cytoplasm with high efficiency. Using this approach, EV acted as a dominant negative inhibitor of STAT5b phosphorylation, arrested cell proliferation, and induced massive apoptosis. Intravenous administration of EV loaded in LPH-PEG-AA led to efficient EV peptide delivery to the tumor in a xenograft mouse model, and multiple injections inhibited tumor growth in a dose-dependent manner. Our findings offer proof-of-concept for an intracellular peptide-mediated cancer therapy that is delivered by carefully designed nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / administration & dosage*
  • ErbB Receptors / metabolism*
  • Female
  • Heparin / administration & dosage
  • Humans
  • Liposomes / administration & dosage
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy
  • Nanoparticles / administration & dosage*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Oligopeptides / administration & dosage*
  • Phosphorylation / drug effects
  • Protamines / administration & dosage
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays


  • Drug Carriers
  • Liposomes
  • Oligopeptides
  • Protamines
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • Heparin
  • ErbB Receptors