Photochemical enhancement of gene delivery to glioblastoma cells is dependent on the vector applied

Anticancer Res. Jan-Feb 2005;25(1A):291-7.

Abstract

Background: Photodynamic therapy (PDT) and gene therapy protocols are separately under clinical evaluation for treatment of brain malignancies. Here, the potential of a novel combination technique, photo-induced delivery of macromolecules and genes to glioblastoma cells, is evaluated.

Materials and methods: The photochemical effect on survival of GaMg and U-87Mg cells after incubation with the protein toxin gelonin, on transfection with a plasmid complexed to poly-L-lysine (PLL), and on transduction with adenovirus serotype 5 (Ad5) and adeno-associated virus type 5 (AAV5) vectors, were studied.

Results: Cytotoxicity of gelonin and gene transfer from plasmid/PLL complexes were considerably improved by photochemical treatment in both cell lines, while the light-inducible effect on Ad5 transduction was most pronounced in U-87Mg. For the first time, photochemical enhancement of AAV transduction is shown. A 4-fold increase in percentage positive cells was detected after photochemical treatment of AAV5-infected GaMg cells. However, in contrast to Ad5, AAV5 transduction of U-87Mg remained unaffected by light treatment, independently of viral dose, light dose and timing of the light treatment relative to the transduction period.

Conclusion: Photochemical treatment is a versatile tool for macromolecular delivery to glioblastoma cells, however, the photochemical effect on gene transfer by viral vectors is highly dependent on the cell line and vector applied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adult
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / therapy*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Photochemotherapy / methods*
  • Plant Proteins / administration & dosage*
  • Plant Proteins / genetics
  • Polylysine / genetics
  • Ribosome Inactivating Proteins, Type 1
  • Transduction, Genetic
  • Transfection

Substances

  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Polylysine
  • GEL protein, Gelonium multiflorum