Home > Publications database > Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery > print

001     893828
005     20210810182032.0
024 7 _ |a 10.3390/pharmaceutics13020295
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082 _ _ |a 610
100 1 _ |a Giesen, Beatriz
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245 _ _ |a Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery
260 _ _ |a Basel
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520 _ _ |a Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of the glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using a bottom-up approach and covered with polymers able to bind CB839 as a Au-polymer-CB839 conjugate. The drug loading efficiency (DLE) was determined using high-performance liquid chromatography and characterization of the CB839-loaded NPs was done with various microscopic and spectroscopic methods. Despite the chemical inertness of CB839, Au NPs were efficient carriers with a DLE of up to 12%, depending on the polymer used. The therapeutic effect of CB839 with and without Au was assessed in vitro in 2D and 3D glioblastoma (GBM) cell models using different assays based on the colony formation ability of GBM stem cells (GSCs). To avoid readout disturbances from the Au metal, viability methods which do not require optical detection were hereby optimized. These showed that Au NP delivery increased the efficacy of CB839 in GSCs, compared to CB839 alone. Fluorescent microscopy proved successful NP penetration into the GSCs. With this first attempt to combine CB839 with Au nanotechnology, we hope to overcome delivery hurdles of this pharmacotherapy and increase bioavailability in target sites.
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700 1 _ |a Nickel, Ann-Christin
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700 1 _ |a Barthel, Juri
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700 1 _ |a Kahlert, Ulf Dietrich
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700 1 _ |a Janiak, Christoph
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773 _ _ |a 10.3390/pharmaceutics13020295
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