Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF-saporin

J Control Release. 2006 Mar 10;111(1-2):165-73. doi: 10.1016/j.jconrel.2005.12.002. Epub 2006 Feb 8.


Epidermal growth factor receptor (EGFR) targeting has become a major field in both cancer research and therapy. In the present study an EGF-saporin affinity toxin has been established and evaluated in two EGFR overexpressing cancer cell lines. The binding of saporin to EGF did not influence the ribosome-inactivating activity of saporin as measured by a luminescence based reticulocyte lysate assay. Control experiments, using untargeted saporin, EGFR-negative cell lines and competition with EGF and anti-EGFR antibody were used to document selective uptake of the affinity toxin. One limitation in administration of macromolecular-drugs is lysosomal degradation. Photochemical internalization (PCI) is a modality for cytosolic release of macromolecules based on photochemical rupture of endocytic membranes and subsequent drug release. It was shown that PCI increases the toxicity of EGF-saporin significantly in EGFR-positive cells. EGF binding to saporin enhanced the PCI-induced cytotoxicity in NuTu-19 cells about 1000-fold when the photochemical treatment alone killed 50% of the cells. In conclusion, PCI of EGF-saporin is a promising method for increasing the efficiency of protein toxin-based cancer therapies. PCI of targeting toxins also exert a triple tumour-selectivity; utilization of an affinity toxin, preferential accumulation of the photosensitizer in neoplastic lesions, and site-directed light activation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biotin / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / metabolism
  • Humans
  • Immunotoxins / chemistry
  • Immunotoxins / pharmacology*
  • Microscopy, Fluorescence
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / pharmacology
  • Ribosomes / drug effects
  • Ribosomes / metabolism
  • Streptavidin / chemistry
  • Time Factors


  • Immunotoxins
  • Protein Synthesis Inhibitors
  • Epidermal Growth Factor
  • Biotin
  • Streptavidin
  • ErbB Receptors