Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex
| العنوان: | Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex |
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| المؤلفون: | Noga Yerushalmi, Shiran Ferber, Paula Ofek, Adva Krivitsky, Galia Tiram, Marcelo Calderón, Ronit Satchi-Fainaro, Rachel Grossman, Fatemeh Sheikhi Mehrabadi, Zvi Ram, Rainer Haag, Sharon Kredo-Russo |
| المصدر: | Nanomedicine |
| بيانات النشر: | Elsevier, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Glycerol, Carrier system, Polymers, Biomedical Engineering, Medicine (miscellaneous), Pharmaceutical Science, Bioengineering, Drug resistance, 03 medical and health sciences, Materials Science(all), Polyglycerol-based polyplex, Cell Movement, Cell Line, Tumor, microRNA, medicine, Animals, Humans, General Materials Science, Cell Proliferation, Drug Carriers, biology, Chemistry, Brain Neoplasms, medicine.disease, MicroRNA-34a, 3. Good health, MicroRNAs, 030104 developmental biology, MicroRNA 34a, Immunology, Toxicity, Cancer research, biology.protein, Molecular Medicine, Original Article, Cyclin-dependent kinase 6, Glioblastoma, Intracellular |
| الوصف: | Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood–brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2–miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2–miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity. Graphical Abstract Schematic representation of aminated polyglycerol-based dPG-NH2–miR-34a polyplex taken-up by glioblastoma cells, inhibiting their proliferation and migration and accumulating selectively at the tumor site in the brain following extravasation via the tumor leaky vessels. |
| اللغة: | English |
| تدمد: | 1549-9642 1549-9634 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c31175418f30458131d2cedc331126d5 http://europepmc.org/articles/PMC5364374 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c31175418f30458131d2cedc331126d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15499642 15499634 |
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