| Self-Assembly of Stable Monomolecular Nucleic Acid Lipid Particles with a Size of 30 nm. | |
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MedLine Citation:
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PMID: 22694262 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The design of efficient nucleic acid complexes is key to progress in genetic research and therapies based on RNA interference. For optimal transport within tissue and across extracellular barriers, nucleic acid carriers need to be small and stable. In this paper we prepare and characterize mono-Nucleic Acid Lipid Particles (mono-NALPs). The particles consist of single short double stranded oligonucleotides or single siRNA molecules each encapsulated within a closed shell of a cationic-zwitterionic lipid bilayer, furnished with an outer polyethylene glycol (PEG) shield. The particles self-assemble by solvent exchange from a solution containing nucleic acid mixed with the four lipid components DOTAP, DOPE, DOPC and DSPE-PEG(2000). Using fluorescence correlation spectroscopy we monitor the formation of mono-NALPs from short double stranded oligonucleotides or siRNA and lipids into monodisperse particles of approximately 30 nm in diameter. Small angle neutron and X-ray scattering and transmission electron microscopy experiments substantiate a micelle-like core-shell structure of the particles. The PEGylated lipid shell protects the nucleic acid core against degradation by nucleases, sterically stabilizes the mono-NALPs against disassembly in collagen networks and prevents non-specific binding to cells. Hence PEG-lipid shielded mono-NALPs are the smallest stable siRNA lipid system possible and may provide a structural design to be build upon for the development of novel nucleic acid delivery systems with enhanced biodistribution in vivo. |
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Authors:
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Sophia Rudorf; Joachim O Radler |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-13 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: - ISSN: 1520-5126 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc 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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