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


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.


CONCLUSIONS
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.
Bonsted
Anette
A
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway. anettbo@ulrik.uio.no
Høgset
Anders
A
Hoover
Frank
F
Berg
Kristian
K
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D010940:Plant Proteins / Q000008:administration & dosage* / Q000235:genetics; D011107:Polylysine / Q000235:genetics; D054789:Ribosome Inactivating Proteins, Type 1; D014161:Transduction, Genetic; D014162:Transfection
D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011107:Polylysine; C025674:GEL protein, Gelonium multiflorum