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@ARTICLE{Giesen:893828,
author = {Giesen, Beatriz and Nickel, Ann-Christin and Barthel, Juri
and Kahlert, Ulf Dietrich and Janiak, Christoph},
title = {{A}ugmented {T}herapeutic {P}otential of {G}lutaminase
{I}nhibitor {CB}839 in {G}lioblastoma {S}tem {C}ells {U}sing
{G}old {N}anoparticle {D}elivery},
journal = {Pharmaceutics},
volume = {13},
number = {2},
issn = {1999-4923},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2021-02867},
pages = {295 -},
year = {2021},
abstract = {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.},
cin = {ER-C-2},
ddc = {610},
cid = {I:(DE-Juel1)ER-C-2-20170209},
pnm = {5351 - Platform for Correlative, In Situ and Operando
Characterization (POF4-535) / 5353 - Understanding the
Structural and Functional Behavior of Solid State Systems
(POF4-535)},
pid = {G:(DE-HGF)POF4-5351 / G:(DE-HGF)POF4-5353},
typ = {PUB:(DE-HGF)16},
pubmed = {33672398},
UT = {WOS:000622975900001},
doi = {10.3390/pharmaceutics13020295},
url = {https://juser.fz-juelich.de/record/893828},
}