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Web Date: November 21, 2011

Fatty Bundles Sneak siRNA Into Cells

Nanotechnology: Lipid nanoparticles offer a new way to deliver therapeutic nucleic acids
Department: Science & Technology
News Channels: Analytical SCENE, Materials SCENE
Keywords: solid lipid nanoparticles, siRNA, sustained release, drug delivery, gene therapy
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Signed, Sealed, Delivered
A nanoparticle decorated with lipids (orange) and other molecules carries siRNA (red) in complex with a positively charged lipid (purple).
Credit: ACS Nano
20111121lnj1_CartoonNanoparticle
 
Signed, Sealed, Delivered
A nanoparticle decorated with lipids (orange) and other molecules carries siRNA (red) in complex with a positively charged lipid (purple).
Credit: ACS Nano
[+]Enlarge
Small Packages
A scanning electron microscope shows the solid lipid nanoparticles that deliver therapeutic molecules.
Credit: ACS Nano
20111121lnj1_SLNPs
 
Small Packages
A scanning electron microscope shows the solid lipid nanoparticles that deliver therapeutic molecules.
Credit: ACS Nano

Inside a cell, small interfering RNAs (siRNAs) can silence genes responsible for disease, making them ideal molecules for gene therapy. But siRNAs have trouble getting there. Now researchers report that they can smuggle the nucleic acids into cells by wrapping them in lipid nanoparticles (ACS Nano, DOI: 10.1021/nn203745n).

Like all nucleic acids, siRNAs are packed with negative charges, so they don’t easily penetrate cells’ hydrophobic membranes. To solve this problem, Richard Zare of Stanford University and his colleagues decided to encapsulate siRNAs in small greasy spheres called solid lipid nanoparticles. But because of the same negative charges, loading siRNAs into lipid nanoparticles is also difficult, says Zare. So the researchers mixed siRNA with a positively charged lipid called 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which masked the nucleic acid’s negative charge and provided a hydrophobic hook to draw the complex into the belly of the nanoparticle.

To test their delivery system, the researchers injected nanoparticles charged with a fluorescently labeled siRNA and DOTAP into the left hind feet of mice and injected the labeled siRNA alone into the right feet. They found that the left feet containing nanoparticles glowed for 11 days, while the right feet without the particles glowed for two. This difference, says Zare, suggests that the nanoparticles protect the siRNA from quick degradation and release the nucleic acids slowly over time—two desirable properties for delivery of gene therapies. Using fluorescence microscopy, the scientists spotted the fluorescent dye inside skin cells from the left feet, confirming the nanoparticles’ ability to sneak siRNA into cells.

Zare’s lab is now working on using their siRNA-carrying nanoparticles to shut down disease-causing genes in mice.

 
Chemical & Engineering News
ISSN 0009-2347
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