دورية أكاديمية
Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA
| العنوان: | Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA |
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| المؤلفون: | Yathindranath, Vinith, Safa, Nura, Sajesh, Babu V., Schwinghamer, Kelly, Vanan, Magimairajan Issai, Bux, Rashid, Sitar, Daniel S., Pitz, Marshall, Siahaan, Teruna J., Miller, Donald W. |
| بيانات النشر: | MDPI |
| سنة النشر: | 2022 |
| المجموعة: | The University of Kansas: KU ScholarWorks |
| مصطلحات موضوعية: | Glioblastoma (GB), Spermidine/spermine N1-acetyltransferase 1 (SAT1), Lipid nanoparticles, siRNA, Microfluidic mixing, Gene therapy, Brain drug delivery, Blood–brain barrier (BBB), Transient modulation, Cadherin peptides, Tumor sensitization |
| الوصف: | Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood–brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | Yathindranath, V.; Safa, N.; Sajesh, B.V.; Schwinghamer, K.; Vanan, M.I.; Bux, R.; Sitar, D.S.; Pitz, M.; Siahaan, T.J.; Miller, D.W. Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA. Cancers 2022, 14, 5179. https://doi.org/10.3390/cancers14215179Test; http://hdl.handle.net/1808/33773Test; orcid:0000-0003-2015-0615; orcid:0000-0001-7250-0627; orcid:0000-0003-1952-5635; PMC9656607 |
| DOI: | 10.3390/cancers14215179 |
| الإتاحة: | https://doi.org/10.3390/cancers14215179Test http://hdl.handle.net/1808/33773Test |
| حقوق: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. ; http://creativecommons.org/licenses/by/4.0Test/ ; openAccess |
| رقم الانضمام: | edsbas.5E9EEFCE |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers14215179 |
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