| Induction of Apoptosis by Survivin Silencing through siRNA Delivery in a Human Breast Cancer Cell Line. | |
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MedLine Citation:
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PMID: 21838308 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Post-transcriptional silencing of anti-apoptotic genes is a promising strategy for cancer therapy, but delivering short interfering RNA (siRNA) molecules against such targets is challenging due to inability of anionic siRNA to cross cellular membranes. Lipid substitution on small molecular weight, non-toxic polyethylenimine (PEI) has been investigated as a promising approach for effective siRNA delivery. In this study, we report on the ability of low molecular, lipid-substituted PEI to deliver siRNA against the anti-apoptotic protein survivin. Toxicity of a library of lipid-substituted PEIs, as well as their siRNA delivery and survivin silencing efficiency were evaluated in MDA-MB-231 human breast cancer cells. A significant increase in cellular delivery of siRNA was observed as a result of lipid substitution. Most significant down-regulation of survivin was established by caprylic acid-substituted polymers, which resulted in significant levels of apoptosis induction and resultant loss of cell viability. Survivin down-regulation prior to anticancer drug treatment decreased the IC50 of several drugs by 50 to 120-fold. Our experiments indicated an effective down-regulation of survivin, a cell protective protein up-regulated in tumor cells, by delivering siRNA with hydrophobically modified PEI. This study introduces a promising delivery system for safe and effective siRNA delivery that will be suitable for further investigation in preclinical animal models. |
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Authors:
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Hamidreza Montazeri Aliabadi; Breanne Landry; Parvin Mahdipoor; Hasan Uludag |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-15 |
Journal Detail:
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Title: Molecular pharmaceutics Volume: - ISSN: 1543-8392 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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