gms | German Medical Science

72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

Increasing the therapeutic potential of novel anti-brain cancer stem cell pharmacotherapy with gold nanotechnology

Steigerung des therapeutischen Potentials neuartiger anti-Hirntumorstammzell-gerichteter Pharmakotherapie mittels Gold-Nanopartikel

Meeting Abstract

  • Beatriz Giesen - University Hospital Düsseldorf, Inorganic chemistry, Düsseldorf, Deutschland
  • presenting/speaker Ann-Christin Nickel - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Daniel Hänggi - University Hospital Düsseldorf, Inorganic Chemistry, Düsseldorf, Deutschland
  • Christof Janiak - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Ulf Dietrich Kahlert - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland; Capital Medial University, Beijing Neurosurgical Institute, Peking, China

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP038

doi: 10.3205/21dgnc326, urn:nbn:de:0183-21dgnc3261

Veröffentlicht: 4. Juni 2021

© 2021 Giesen et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe



Objective: Stem cells in glioblastoma (GBM) are considered to be a main contributor for the high levels of therapy resistance of the disease. The identification of metabolic dependencies of those GBM stem cells (GSCs), such as glutaminase 1 activity, opens a new area for future management of neuro oncology patients. We sought to optimise therapeutic potential of GLS1 inhibitor CB839, previously shown to possess promising anti-GSC activity, by improving its target delivery using gold nanoparticles (Au NPs)

Methods: Au NPs were synthesized using a bottom-up approach and covered with various polymers, which allowed the attachment of the inhibitor via physical adsorption. Synthesis and quality control assays include transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, high performance liquid chromatography amongst others. The efficacy of the CB839 inhibitor with and without the Au carriers was assessed in a collection of GBM neurospheres known to recapitulate core pathophysiological properties of the disease. Mode of action and functional validation assays of our drug development project include colony formation, Western Blot-based protein analysis as well as fluorecence stainings.

Results: Au NPs proved to be an efficient carrier for CB839 with a drug loading efficiency of up to 12%, a values proofing solid non-covalence atomic binding. Optical verification proofed efficient penetration of NP into the GSCs. A delivery with NPs resulted in an increased therapeutic effect of the drug of up to 45% increase, compared to the drug alone, as assessed by colony formation assay. However, NP-assisted treatment did not alter total GLS1 protein of the cells as compared to control counterparts.

Conclusion: Au NPs are potential carriers to deliver anti-metabolic inhibitor CB839 into therapy resistant GSCs more efficiently leading to enhanced efficacy of this promising pharmacotherapy. However, mechanistic explanation of the observed effect on molecular level, such as GLS1 enzymatic activity assessment or quantification of intracellular drug release kinetics are ongoing to comprehensively characterize the mode of action of our NP-drug conjugate. Given the amendable nature of our NP synthesis and functionalization procedures, we hypothesize that our results can be the basis for additional nanomedicine approaches in neuro oncology and beyond.