Cell type-specific delivery of short interfering RNAs by dye-functionalised theranostic nanoparticles

Adrian T. Press, Anja Traeger, Christian Pietsch, Alexander Mosig, Michael Wagner, Mark G. Clemens, Nayla Jbeily, Nicole Koch, Michael Gottschaldt, Nicolas Bézière, Volodymyr Ermolayev, Vasilis Ntziachristos, Jürgen Popp, Michael M. Kessels, Britta Qualmann, Ulrich S. Schubert and Michael Bauer ()
Additional contact information
Adrian T. Press: Center for Sepsis Control & Care (CSCC), Jena University Hospital
Anja Traeger: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Christian Pietsch: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Alexander Mosig: Center for Sepsis Control & Care (CSCC), Jena University Hospital
Michael Wagner: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Mark G. Clemens: Center for Sepsis Control & Care (CSCC), Jena University Hospital
Nayla Jbeily: Center for Sepsis Control & Care (CSCC), Jena University Hospital
Nicole Koch: Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University
Michael Gottschaldt: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Nicolas Bézière: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München
Volodymyr Ermolayev: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München
Vasilis Ntziachristos: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München
Jürgen Popp: Center for Sepsis Control & Care (CSCC), Jena University Hospital
Michael M. Kessels: Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University
Britta Qualmann: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Ulrich S. Schubert: Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena
Michael Bauer: Center for Sepsis Control & Care (CSCC), Jena University Hospital

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Efficient delivery of short interfering RNAs reflects a prerequisite for the development of RNA interference therapeutics. Here, we describe highly specific nanoparticles, based on near infrared fluorescent polymethine dye-derived targeting moieties coupled to biodegradable polymers. The fluorescent dye, even when coupled to a nanoparticle, mimics a ligand for hepatic parenchymal uptake transporters resulting in hepatobiliary clearance of approximately 95% of the dye within 45 min. Body distribution, hepatocyte uptake and excretion into bile of the dye itself, or dye-coupled nanoparticles can be tracked by intravital microscopy or even non-invasively by multispectral optoacoustic tomography. Efficacy of delivery is demonstrated in vivo using 3-hydroxy-3-methyl-glutaryl-CoA reductase siRNA as an active payload resulting in a reduction of plasma cholesterol levels if siRNA was formulated into dye-functionalised nanoparticles. This suggests that organ-selective uptake of a near infrared dye can be efficiently transferred to theranostic nanoparticles allowing novel possibilities for personalised silencing of disease-associated genes.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6565

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DOI: 10.1038/ncomms6565

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