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.