Glioblastoma Targeted Gene Therapy Based on pEGFP/p53-Loaded Superparamagnetic Iron Oxide Nanoparticles
Seyed Noureddin Nematollahi-Mahani,
Background: Blood-brain barrier (BBB) separates the neural tissue from circulating blood
because of its high selectivity. This study focused on the in vitro application of magnetic nanoparticles
to deliver Tp53 as a gene of interest to glioblastoma (U87) cells across a simulated BBB model
that comprised KB cells.
Material and Method: After magnetic and non-magnetic nanoparticles were internalized by KB cells,
their location in these cells was examined by transmission electron microscopy. Transfection efficiency
of DNA to U87 cells was evaluated by fluorescence microscopy, real time PCR, flowcytometry,
and Western immuno-blotting. When a magnetic field was applied, a large number of magnetic
nanoparticles accumulated in KB cells, appearing as black dots scattered in the cytoplasm of cells.
Fluorescence microscope examination showed that transfection of the DNA to U87 target cells was
highest in cells treated with magnetic nanoparticles and exposed to a magnetic field. Also it was reflected
in significantly increased mRNA level while the p53 protein level was decreased.
Conclusion: It could be concluded that a significant increase in total apoptosis was induced in cells
by magnetic nanoparticles, coupled with exposure to a magnetic force (p ≤0.01) as compared with
cells that were not exposed to magnetism.
Keywords: Blood-brain barrier, brain cancer, magnetic nanoparticles, molecular medicine, p53 signaling pathway, targeted
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