Scientists at the Friedrich Schiller University Jena (FSU Jena; Germany) and colleagues have produced highly specific fluorescent nanoparticles that, with near-infrared (NIR) fluorescent dye, can be guided to the liver or kidney and deliver their payload of active ingredients directly to the targeted tissue. Also, they enable tracking of the transport processes by intravital microscopy or, in a noninvasive way, by multispectral optoacoustic tomography.
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Reduction of cholesterol production induced by small interfering ribonucleic acid (siRNA) served as the proof of principle for the scientists' work. The nanoparticles are based on polymers and marked with NIR fluorescent dyes and loaded with siRNA.
|Highly specific nanoparticles that were produced at Friedrich Schiller University Jena. (Photo courtesy of Jan-Peter Kasper/FSU Jena)|
"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. At the same time, this route can easily be tracked by optical methods with the aid of the dyes," describes intensive care physician Prof. Dr. Michael Bauer. His research team was also able to show that the dye is specifically absorbed by a specific cellular transporter of the liver epithelial cells and taken up into the cells.
In this way, the siRNA load is exclusively released in the target cells. The specifically functionalized nano-containers have been designed and produced in the laboratories of the Jena Center for Soft Matter (JCSM) of FSU Jena.
"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," states Prof. Dr. Ulrich S. Schubert, director of the JCSM.
|Schematic of a nanoparticle loaded with a drug in the core (purple) and a specific dye marker at the surface of the particle (blue dots). (Image courtesy of JCSM/SmartDyeLivery GmbH)|
With the possibility to test the non-coupled dyes in advance and to switch off genes that are associated with illnesses, the principle offers new approaches to personalized medicine. In the newly founded SmartDyeLivery GmbH, the scientists want to further develop the technology to put it into practical use in the clinical environment, especially in cases of acute septic infections.
In their study, the researchers loaded the nanoparticles with targeting dyes attached with siRNA-molecules. The siRNA molecules interfered with cholesterol production in hepatocytes, which resulted a clear reduction in the cholesterol level in the blood of test animals.
Full details of the work appear in the journal Nature Communications; for more information, please visit http://dx.doi.org/10.1038/ncomms6565.
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