Characterization of Cationic Bolaamphiphile Vesicles for siRNA Delivery into Tumors and Brain
| العنوان: | Characterization of Cationic Bolaamphiphile Vesicles for siRNA Delivery into Tumors and Brain |
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| المؤلفون: | Jacqueline Salotti, Kirill A. Afonin, Mary Popov, Eliahu Heldman, Mathias Viard, Charles Linder, Taejin Kim, Peter F. Johnson, Kshitij Gupta, Bruce A. Shapiro |
| المصدر: | Molecular Therapy: Nucleic Acids, Vol 20, Iss, Pp 359-372 (2020) Molecular Therapy. Nucleic Acids |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Small interfering RNA, Cell, Endocytosis, Transfection, Molecular Dynamics, Article, 03 medical and health sciences, Bolaamphiphiles, 0302 clinical medicine, Drug Discovery, medicine, Gene silencing, Gene Silencing, Vesicles, Targeting, Chemistry, Vesicle, Blood Brain Barrier (BBB), lcsh:RM1-950, RNA Nanotechnology, Cell biology, Delivery Systems, 030104 developmental biology, medicine.anatomical_structure, lcsh:Therapeutics. Pharmacology, Transcytosis, 030220 oncology & carcinogenesis, siRNA, Cancer cell, Molecular Medicine |
| الوصف: | Small interfering RNAs (siRNAs) are potential therapeutic substances due to their gene silencing capability as exemplified by the recent approval by the US Food and Drug Administration (FDA) of the first siRNA therapeutic agent (patisiran). However, the delivery of naked siRNAs is challenging because of their short plasma half-lives and poor cell penetrability. In this study, we used vesicles made from bolaamphiphiles (bolas), GLH-19 and GLH-20, to investigate their ability to protect siRNA from degradation by nucleases while delivering it to target cells, including cells in the brain. Based on computational and experimental studies, we found that GLH-19 vesicles have better delivery characteristics than do GLH-20 vesicles in terms of stability, binding affinity, protection against nucleases, and transfection efficiency, while GLH-20 vesicles contribute to efficient release of the delivered siRNAs, which become available for silencing. Our studies with vesicles made from a mixture of the two bolas (GLH-19 and GLH-20) show that they were able to deliver siRNAs into cultured cancer cells, into a flank tumor and into the brain. The vesicles penetrate cell membranes and the blood-brain barrier (BBB) by endocytosis and transcytosis, respectively, mainly through the caveolae-dependent pathway. These results suggest that GLH-19 strengthens vesicle stability, provides protection against nucleases, and enhances transfection efficiency, while GLH-20 makes the siRNA available for gene silencing. Graphical Abstract |
| اللغة: | English |
| تدمد: | 2162-2531 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f19b5cd6a2273a9e9eb50e6166440cc8 http://www.sciencedirect.com/science/article/pii/S2162253120300883 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f19b5cd6a2273a9e9eb50e6166440cc8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21622531 |
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