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Nat Commun. 2014 Dec 3;5:5565. doi: 10.1038/ncomms6565.

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

Author information

1
1] Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany [2] Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Phiolophenweg 7, 07743 Jena, Germany.
2
1] Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Phiolophenweg 7, 07743 Jena, Germany [2] Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743 Jena, Germany.
3
1] Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany [2] Molecular Hemostaseology, Jena University Hospital, Bachstraße 18, 07743 Jena, Germany.
4
1] Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany [2] Department of Biological Sciences and Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
5
Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
6
Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany.
7
Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
8
1] Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany [2] Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Phiolophenweg 7, 07743 Jena, Germany [3] Leibniz Institute for Photonic Technology Jena, Albert-Einstein-Strasse 9, 07745 Jena, Germany [4] Abbe Center of Photonics, Friedrich Schiller University, Max-Wien-Platz 1, 07743 Jena, Germany.
9
1] Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Phiolophenweg 7, 07743 Jena, Germany [2] Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany.
10
1] Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany [2] Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Phiolophenweg 7, 07743 Jena, Germany [3] Abbe Center of Photonics, Friedrich Schiller University, Max-Wien-Platz 1, 07743 Jena, Germany.

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.

PMID:
25470305
PMCID:
PMC4268698
DOI:
10.1038/ncomms6565
[Indexed for MEDLINE]
Free PMC Article

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