| Autor: |
Knauer N; Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia.; Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Medical Center Düsseldorf, 40225 Düsseldorf, Germany., Meschaninova M; Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 Novosibirsk, Russia., Muhammad S; Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Medical Center Düsseldorf, 40225 Düsseldorf, Germany., Hänggi D; Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Medical Center Düsseldorf, 40225 Düsseldorf, Germany., Majoral JP; Laboratoire de Chimie de Coordination, CNRS, 205 Route de Narbonne, CEDEX 04, 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., Kozlov V; Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia., Apartsin EK; Univ. Bordeaux, CNRS, Bordeaux INP, CBMN, UMR 5248, 33600 Pessac, France. |
| Abstrakt: |
Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation. |
