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PEI-coated Fe3O4 nanoparticles enable efficient delivery of therapeutic siRNA targeting REST into glioblastoma cells
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Wang, Rui, Degirmenci, Volkan, Xin, Hongchuan, Li, Ying, Wang, Liping, Chen, Jiayu, Hu, Xiaoyu and Zhang, Dianbao (2018) PEI-coated Fe3O4 nanoparticles enable efficient delivery of therapeutic siRNA targeting REST into glioblastoma cells. International Journal of Molecular Sciences, 19 (8). 2230. doi:10.3390/ijms19082230 ISSN 1422-0067.
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Official URL: https://doi.org/10.3390/ijms19082230
Abstract
Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe3O4 NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe3O4 nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | R Medicine > RS Pharmacy and materia medica | |||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Nanoparticles, Brain -- Tumors -- Treatment, Iron oxides, Small interfering RNA, Gene therapy | |||||||||||||||
Journal or Publication Title: | International Journal of Molecular Sciences | |||||||||||||||
Publisher: | MDPI AG | |||||||||||||||
ISSN: | 1422-0067 | |||||||||||||||
Official Date: | 31 July 2018 | |||||||||||||||
Dates: |
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Volume: | 19 | |||||||||||||||
Number: | 8 | |||||||||||||||
Article Number: | 2230 | |||||||||||||||
DOI: | 10.3390/ijms19082230 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | ** From Crossref via Jisc Publications Router. | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 17 September 2018 | |||||||||||||||
Date of first compliant Open Access: | 17 September 2018 | |||||||||||||||
RIOXX Funder/Project Grant: |
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