Fluorescent Dyes Target Disease Genes

Fluorescent dye-coated nanoparticles could be used to target and turn off disease-related genes.

To test this concept, a team of researchers from Germany and the U.S. developed nanoparticles that interfered with cholesterol production in the livers of test animals.

The biodegradable polymer nanoparticles were covered with near-infrared fluorescent polymethine dyes that made it possible to track the nanoparticles’ movements in vivo using intravital microscopy or noninvasive multispectral optoacoustic tomography.

But the dyes also play another key function: Because they mimic a cellular transporter of liver epithelial cells, the liver absorbs them readily.

A scheme of a nanoparticle loaded with drugs in the core (purple) and specific dye markers at the surface (blue dots). Courtesy of JCSM/SmartDyeLivery GmbH.

“Depending on the chemical structure of the dye, the particles are filtered out of the blood either via the kidney tissue or via liver cells,” said professor Dr. Michael Bauer of the Jena University Hospital Center for Sepsis Control and Care. “At the same time this route can easily be tracked by optical methods with the aid of the dyes.”

Also contained in the nanoparticles were small interfering RNA molecules (siRNA), which prevent certain genes from producing proteins — in this case, they prevented hepatocytes from releasing cholesterol into the bloodstream. The nanoparticles are designed to release siRNA only when they reach the targeted tissue to avoid harming healthy cells.

“This method can be regarded as a kind of toolbox for a multitude of different siRNA nanotransporters, which can ensure the targeted ‘switch-off’ of specific protein biosynthesis in different cell types,” said professor Dr. Ulrich S. Schubert of the Jena Center for Soft Matter at Friedrich Schiller University, where the nanoparticles were created.

Through the startup SmartDyeLivery GmbH, the researchers plan to develop the technology for clinical use, especially in cases of acute septic infections.

The work was published in Nature Communications (doi: 10.1038/ncomms6565).

For more information, visit www.uni-jena.de.