Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and Activation of Photodynamic Therapy Drug in Glioblastomas

Mol Pharm. 2015 Sep 8;12(9):3250-60. doi: 10.1021/acs.molpharmaceut.5b00216. Epub 2015 Aug 24.


Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides has been proposed to address intratumoral heterogeneity of glioblastomas that overexpress multiple cell surface receptors to ultimately improve therapeutic efficacy. AuNPs conjugated with peptides against both the epidermal growth factor and transferrin receptors and loaded with the photosensitizer phthalocyanine 4 (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ∼41 nm improved both specificity and worked synergistically to decrease time of maximal accumulation in human glioma cells that overexpressed two cell surface receptors as compared to cells that overexpressed only one. Enhanced cellular association and increased cytotoxicity were achieved. In vivo studies show notable accumulation of these agents in the brain tumor regions.

Keywords: Pc 4; epidermal growth factor; glioblastoma; gold nanoparticles; transferrin.

Publication types

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

MeSH terms

  • Animals
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • ErbB Receptors / antagonists & inhibitors*
  • Glioblastoma / drug therapy*
  • Gold / chemistry*
  • Humans
  • Indoles / pharmacology*
  • Metal Nanoparticles / chemistry*
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Receptors, Transferrin / antagonists & inhibitors*
  • Theranostic Nanomedicine*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Drug Carriers
  • Indoles
  • Peptide Fragments
  • Photosensitizing Agents
  • Receptors, Transferrin
  • phthalocyanine Pc 4
  • Gold
  • EGFR protein, human
  • ErbB Receptors