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Press, A.T.* ; Traeger, A.* ; Pietsch, C.* ; Mosig, A.* ; Wagner, M.* ; Clemens, M.G.* ; Jbeily, N.* ; Koch, N.* ; Gottschaldt, M.* ; Bézière, N. ; Ermolayev, V. ; Ntziachristos, V. ; Popp, J.* ; Kessels, M.M.* ; Qualmann, B.* ; Schubert, U.S.* ; Bauer, M.*

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

Nat. Commun. 5:5565 (2014)

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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.

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