| Autor: |
Knauer N; Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia.; Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany., Arkhipova V; Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia., Li G; Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100054, China., Hewera M; Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany., Pashkina E; Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia., Nguyen PH; Center of Molecular Medicine, Department I of Internal Medicine, University of Cologne, 50923 Cologne, Germany., Meschaninova M; Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia., Kozlov V; Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia., Zhang W; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100054, China.; China National Clinical Research Center for Neurological Diseases, Beijing 100053, China.; Chinese Glioma Genome Atlas Network (CGGA), Asian Glioma Genome Atlas Network (AGGA), Beijing 100070, China., Croner RS; Molecular and Experimental Surgery, Clinic for General-, Visceral-, Vascular-, and Transplant-Surgery, Medical Faculty, University Hospital Magdeburg, 39120 Magdeburg, Germany., Caminade AM; Chinese Glioma Genome Atlas Network (CGGA), Asian Glioma Genome Atlas Network (AGGA), Beijing 100070, China., Majoral JP; Chinese Glioma Genome Atlas Network (CGGA), Asian Glioma Genome Atlas Network (AGGA), Beijing 100070, China., Apartsin EK; Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.; Laboratoire de Chimie de Coordination CNRS, 31077 Toulouse, France., Kahlert UD; Molecular and Experimental Surgery, Clinic for General-, Visceral-, Vascular-, and Transplant-Surgery, Medical Faculty, University Hospital Magdeburg, 39120 Magdeburg, Germany. |
| Abstrakt: |
Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development. |
