CD133-Functionalized Gold Nanoparticles as a Carrier Platform for Telaglenastat (CB-839) against Tumor Stem Cells

International Journal of Molecular Sciences

Ann-Christin Nickel¹  Sven G. Meuth²  Elham Poonaki²  Mehdi Shafiee Ardestani³  Ali Gorji⁴  Lars Rademacher⁵  Christoph Janiak⁵  Marilyn Kaul⁵  Evgeny Apartsin⁶  Ulf Dietrich Kahlert⁷ 

[1] Clinic for Neurosurgery, Heinrich-Heine-University, 40225 Düsseldorf, Germany;Department of Neurology, Faculty of Medicine, Heinrich-Heine-University, 40225 Düsseldorf, Germany;Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1416634793, Iran;Epilepsy Research Center, Department of Neurosurgery and Department of Neurology, Westfälische Wilhelms-Universität, 48149 Münster, Germany;Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-University, 40204 Düsseldorf, Germany;Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia;Molecular and Experimental Surgery, University Clinic for General-, Visceral-, Vascular- and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, 39120 Magdeburg, Germany;

关键词: cancer stem cells;    nanomedicine;    glutaminase;    onco-metabolism;    CD133;   

DOI  :  10.3390/ijms23105479

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown