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CD133-Functionalized Gold Nanoparticles as a Carrier Platform for Telaglenastat (CB-839) against Tumor Stem Cells.
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- المؤلفون: Poonaki, Elham1,2,3 (AUTHOR) ; Nickel, Ann-Christin4 (AUTHOR) ; Shafiee Ardestani, Mehdi5 (AUTHOR) ; Rademacher, Lars2 (AUTHOR) ; Kaul, Marilyn2 (AUTHOR); Apartsin, Evgeny6,7 (AUTHOR) ; Meuth, Sven G.1 (AUTHOR) ; Gorji, Ali8,9 (AUTHOR) ; Janiak, Christoph2 (AUTHOR) ; Kahlert, Ulf Dietrich3 (AUTHOR)
- المصدر:
International Journal of Molecular Sciences. May2022, Vol. 23 Issue 10, p5479-5479. 15p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
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. [ABSTRACT FROM AUTHOR]
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