| Effect of cholesterol nanodomains on the targeting of lipid-based gene delivery in cultured cells. | |
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MedLine Citation:
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PMID: 20568694 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Targeted gene delivery offers immense potential for clinical applications. Liposomes decorated with targeting ligands have been extensively used for both in vitro and in vivo gene delivery. Lipoplexes with high cholesterol content that result in cholesterol domain formation within the complexes have been shown to exhibit enhanced transfection in vitro and resistance to serum-induced aggregation. In the present study, folate was employed as a targeting ligand that was conjugated with either cholesterol or a diacyl lipid (DSPE), and these conjugates were incorporated into lipoplexes formulated with DOTAP/cholesterol (wt/wt: 31/69) that are known to possess cholesterol nanodomains. Cellular uptake and transfection of these lipoplexes in the presence of 50% serum were examined when the ligand was located within or excluded from the cholesterol nanodomain. Lipoplexes with folate-cholesterol exhibited a 50-fold increase in transfection compared to those with folate-DSPE, while the cellular uptake level is only 40% of that with folate-DSPE. These results indicate that the presence of the ligand within the cholesterol domain promotes more productive transfection in cultured cells, and intracellular trafficking of the lipoplexes after entry into cells plays a crucial role in gene delivery. |
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Authors:
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Long Xu; Thomas J Anchordoquy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 7 ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-11-24 Revised Date: 2012-03-21 |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 1311-7 Citation Subset: IM |
Affiliation:
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School of Pharmacy, University of Colorado Denver, 12700 East 19th Avenue, Aurora, Colorado 80045, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Calorimetry, Differential Scanning Cell Line, Tumor Cholesterol / chemistry* Fatty Acids, Monounsaturated / chemistry Flow Cytometry Folic Acid / chemistry Gene Transfer Techniques* Humans Liposomes / chemistry*, metabolism* Phosphatidylethanolamines / chemistry Quaternary Ammonium Compounds / chemistry Scattering, Radiation |
| Grant Support | |
ID/Acronym/Agency:
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EB0005476-01A2/EB/NIBIB NIH HHS; R01 EB005476-01A2/EB/NIBIB NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Monounsaturated; 0/Liposomes; 0/Phosphatidylethanolamines; 0/Quaternary Ammonium Compounds; 113669-21-9/1,2-dioleoyloxy-3-(trimethylammonium)propane; 4537-76-2/1,2-distearoylphosphatidylethanolamine; 57-88-5/Cholesterol; 59-30-3/Folic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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