title: Cell type-specific delivery of short interfering RNAs by dye-functionalised theranostic nanoparticles.
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.
authors.affiliation: 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.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Press
authors.affiliation: 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.
authors.forename: Anja
authors.initials: A
authors.lastname: Traeger
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Pietsch
authors.affiliation: 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.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mosig
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
authors.affiliation: Center for Sepsis Control &Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Nayla
authors.initials: N
authors.lastname: Jbeily
authors.affiliation: Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Koch
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottschaldt
authors.affiliation: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bézière
authors.affiliation: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Ermolayev
authors.affiliation: Chair for Biological and Medical Imaging, Technical University Munich and Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: 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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Popp
authors.affiliation: Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kessels
authors.affiliation: 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.
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
authors.affiliation: 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.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000378:metabolism*; D057809:HEK293 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007211:Indoles / Q000378:metabolism*; D053758:Nanoparticles / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats
chemical_list: D005456:Fluorescent Dyes; D007211:Indoles; D034741:RNA, Small Interfering; C098209:VPM chloride; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases