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Published on: May 2, 2016
CD133-Functionalized Gold Nanoparticles as a Carrier Platform for Telaglenastat (CB-839) against Tumor Stem Cells
Elham Poonaki1,2,3, Ann-Christin Nickel4, Mehdi Shafiee Ardestani5
1Department of Neurology, Faculty of Medicine, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Abstract:
The failure of a long-lasting curative therapeutic benefit of currently applied chemotherapies against malignant cancers is suggested to be caused by the ineffectiveness of such interventions on cancer stem cells (CSCs). CD133/AC133 is a cell surface protein previously shown to have potential to identify CSCs in various tumors, including brain tumors. Moreover, an increase in the rate of cellular metabolism of glutamine and glucose are contributors to the fast cellular proliferation of some high-grade malignancies. Inhibition of glutaminolysis by utilizing pharmacological inhibitors of the enzyme glutaminase 1 (GLS1) can be an effective anti-CSC strategy. In this study, the clinical-stage GLS1 inhibitor Telaglenastat (CB-839) was loaded into PEGylated gold nanoparticles equipped with the covalently conjugated CD133 aptamer (Au-PEG-CD133-CB-839) and exposed to a collection of CD133-positive brain tumor models in vitro. Our results show that Au-PEG-CD133-CB-839 significantly decreased the viability of CD133-postive cancer cells in a dose-dependent manner, which was higher as compared to the effects of treatment of the cells with the individual components of the assembled nanodrug. Interestingly, the treatment effect was observed in glioblastoma stem cells modeling different transcriptomic subtypes of the disease. The presented platform is the fundament for subsequent target specificity characterization and in vivo application.
Insights
Targeted nanoparticles delivering a glutaminase 1 inhibitor show promise against brain cancer stem cells (CSCs). This novel nanodrug effectively reduced the viability of CD133-positive cancer cells, offering a potential new strategy for treating malignant brain tumors.
Area of Science:
- Oncology
- Nanomedicine
- Biotechnology
Background:
- Chemotherapy resistance in malignant cancers is linked to cancer stem cells (CSCs).
- CD133 is a cell surface marker identifying CSCs in brain tumors.
- Increased glutamine and glucose metabolism fuels high-grade malignancy proliferation.
Purpose of the Study:
- To develop a targeted nanodrug delivery system for inhibiting glutaminase 1 (GLS1) in brain CSCs.
- To evaluate the efficacy of Telaglenastat-loaded CD133-aptamer-conjugated gold nanoparticles (Au-PEG-CD133-CB-839) against CD133-positive brain tumor models.
Main Methods:
- Fabrication of PEGylated gold nanoparticles functionalized with a CD133 aptamer and loaded with Telaglenastat (CB-839).
- In vitro exposure of CD133-positive brain tumor models, including glioblastoma stem cells, to the assembled nanodrug.
- Assessment of cell viability and comparison with individual component treatments.
Main Results:
- Au-PEG-CD133-CB-839 significantly reduced the viability of CD133-positive cancer cells in a dose-dependent manner.
- The nanodrug demonstrated superior efficacy compared to its individual components.
- Effective treatment was observed across different transcriptomic subtypes of glioblastoma stem cells.
Conclusions:
- The developed Au-PEG-CD133-CB-839 platform shows significant potential as an anti-CSC strategy for brain tumors.
- Targeted inhibition of glutaminolysis via this nanodrug offers a promising therapeutic avenue.
- Further studies for target specificity and in vivo application are warranted.
