Dually Modified Cellulose as a Non-Viral Vector for the Delivery and Uptake of HDAC3 siRNA
Juliana Hülsmann,
Henry Lindemann,
Jamila Wegener,
Marie Kühne,
Maren Godmann,
Andreas Koschella,
Sina M. Coldewey,
Thomas Heinze,
Thorsten Heinzel
Affiliations
Juliana Hülsmann
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany
Henry Lindemann
Institute for Organic Chemistry and Macromolecular Chemistry, Center of Excellence for Polysaccharide Research, Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany
Jamila Wegener
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
Marie Kühne
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany
Maren Godmann
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany
Andreas Koschella
Institute for Organic Chemistry and Macromolecular Chemistry, Center of Excellence for Polysaccharide Research, Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany
Sina M. Coldewey
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
Thomas Heinze
Institute for Organic Chemistry and Macromolecular Chemistry, Center of Excellence for Polysaccharide Research, Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany
Thorsten Heinzel
Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany
RNA interference can be applied to different target genes for treating a variety of diseases, but an appropriate delivery system is necessary to ensure the transport of intact siRNAs to the site of action. In this study, cellulose was dually modified to create a non-viral vector for HDAC3 short interfering RNA (siRNA) transfer into cells. A guanidinium group introduced positive charges into the cellulose to allow complexation of negatively charged genetic material. Furthermore, a biotin group fixed by a polyethylene glycol (PEG) spacer was attached to the polymer to allow, if required, the binding of targeting ligands. The resulting polyplexes with HDAC3 siRNA had a size below 200 nm and a positive zeta potential of up to 15 mV. For N/P ratio 2 and higher, the polymer could efficiently complex siRNA. Nanoparticles, based on this dually modified derivative, revealed a low cytotoxicity. Only minor effects on the endothelial barrier integrity and a transfection efficiency in HEK293 cells higher than Lipofectamine 2000TM were found. The uptake and release of the polyplexes were confirmed by immunofluorescence imaging. This study indicates that the modified biopolymer is an auspicious biocompatible non-viral vector with biotin as a promising moiety.
