TY - CONF A1 - Sieverling, N. A1 - Niclasen, M. A1 - Thünemann, Andreas A1 - Möhwald, H. T1 - Non-viral Gene Vectors T2 - Fachtagung des Max-Planck-Instituts für Kolloid- und Grenzflächenforschung und des Fraunhofer Instituts für Angewandte Polymerforschung, Surfactant-directed Complex Formation in Supramolecular Chemistry T2 - Fachtagung des Max-Planck-Instituts für Kolloid- und Grenzflächenforschung und des Fraunhofer Instituts für Angewandte Polymerforschung, Surfactant-directed Complex Formation in Supramolecular Chemistry CY - Potsdam, Germany DA - 2004-01-09 PY - 2004 AN - OPUS4-4986 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Sieverling, N. A1 - Niclasen, M. A1 - Weiss, S. A1 - Rudolph, C. A1 - Thünemann, Andreas A1 - Möhwald, H. T1 - Sugar-Conjugates for the Receptor-Mediated Gene Transfer T2 - Makromolekulares Kolloquium Freiburg T2 - Makromolekulares Kolloquium Freiburg CY - Freiburg, Germany DA - 2005-02-24 PY - 2005 AN - OPUS4-7493 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Weiss, S. I. A1 - Sieverling, N. A1 - Niclasen, M. A1 - Maucksch, Ch. A1 - Thünemann, Andreas A1 - Möhwald, H. A1 - Reinhardt, D. A1 - Rosenecker, J. A1 - Rudolph, C. T1 - Uronic acids functionalized polyethyleneimine (PEI)-polyethyleneglycol (PEG)-graft-copolymers as novel synthetic gene carriers JF - Biomaterials N2 - In this study, we investigated galacturonic (GalAc)- and mannuronic (ManAc) acids as novel targeting ligands for receptor-mediated gene delivery. GalAc and ManAc were coupled to either polyethyleneimine (PEI) or PEI–polyethyleneglycol (PEG). Furthermore, lactobionic acid (LacAc), which comprises a GalAc-related carbohydrate ring, was coupled to each of the polymers through its open-chain gluconic acid moiety. The molar mass distributions of the polymers were characterized by analytical ultracentrifugation and size exclusion chromatography. PEI-conjugate–pDNA complexes were transfected into HepG2-, HeLa-, and 16HBE14o--cells. Gene expression mediated by GalAc- and LacAc-functionalized PEI-conjugates was lower than for PEI. In contrast, gene expression mediated by ManAc-functionalized PEI-conjugates was up to three orders of magnitude higher than for the other tested PEI-conjugates, in particular for negatively charged gene vectors at low N/P ratios, independent of the cell line. Pre-incubation of cells with an excess of ManAc before transfection significantly inhibited transfection rates only for ManAc-functionalized PEI-conjugates. Coupling of methyl-α-D-mannuronic acid to PEI resulted in significantly lower transfection rates than for ManAc-PEI based complexes. Together with fluorescence microscopy images of fluorescein-labelled ManAc-functionalized dextrans and FACS analyses of cells, these results demonstrate that receptor-mediated endocytosis of ManAc–PEI-conjugate–pDNA complexes via ManAc-specific receptors was involved in gene transfer. In conclusion, ManAc-modification of PEI-polymers represents a novel strategy for receptor-mediated gene delivery which could be promising for in vivo application. KW - Gene therapy KW - Gene transfer KW - Polyethylene oxide KW - Nanoparticle PY - 2006 DO - https://doi.org/10.1016/j.biomaterials.2005.11.011 SN - 0142-9612 VL - 27 IS - 10 SP - 2302 EP - 2312 PB - Elsevier CY - Oxford AN - OPUS4-11678 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bruzzano, S. A1 - Sieverling, N. A1 - Wieland, Ch. A1 - Jaeger, W. A1 - Thünemann, Andreas A1 - Springer, J. T1 - Cationic polymer grafted starch from nonsymmetrically substituted macroinitiators JF - Macromolecules N2 - The aim of this work was the synthesis of starch macroinitiators for cationic polymer grafted starches that: (i) are free of cationic homopolymer, and (ii) display a high degree of conversion of the cationic monomer. We show that this can be achieved by a free-radical polymerization reaction using the cationic monomer N-methacryloyloxyethyl-N,N-dimethyl-N-benzylammonium chloride (MADAM-BQ) and a new starch-based macroazoinitiator. For this purpose, the acid chloride of 4-tert-butylazo-4-cyanovaleric acid was synthesized and bound covalently to starch (predominantly in the C6 position) to form a nonsymmetrically substituted macroinitiator that was used to polymerize MADAM-BQ in aqueous media. Essentially no MADAM-BQ homopolymer was formed. The initiator decomposes thermally to starch radicals of high reactivity and low-molar mass radicals that do not initiate polymerization. The reason for the different reactivities of the radicals is presumably due to the nonsymmetric constitution of the starch-bound azo groups. The graft polymerization of MADAM-BQ in aqueous solution performs according to an ideal overall kinetic. The structure of the synthesized starch-graft-poly(MADAM-BQ) products is similar to that of block copolymers because of the low radical efficiency of the starch initiators in aqueous solution. Especially, starch substrates with a higher content of azo groups did not lead to graft products with shorter graft distances because the state of solution of these macroinitiators becomes worse and aggregation occurs with an increasing degree of substitution. KW - Starch KW - Azo macroinitiators PY - 2005 DO - https://doi.org/10.1021/ma048063f SN - 0024-9297 SN - 1520-5835 VL - 38 SP - 7251 EP - 7261 PB - American Chemical Society CY - Washington, DC AN - OPUS4-10536 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Rudolph, C. A1 - Sieverling, N. A1 - Schillinger, U. A1 - Lesina, E. A1 - Plank, C. A1 - Thünemann, Andreas A1 - Schönberger, H. A1 - Rosenecker, J. T1 - Thyroid hormone (T3)-modification of polyethyleneglycol (PEG)-polyethyleneimine (PEI) graft copolymers for improved gene delivery to hepatocytes JF - Biomaterials N2 - Targeting of gene vectors to liver hepatocytes could offer the opportunity to cure various acquired and inherited diseases. Efficient gene delivery to the liver parenchyma has been obscured from efficient targeting of hepatocytes. Here we show that the thyroid hormone, triiodothyronine (T3), can be used to improve the gene transfer efficiency of nonviral gene vectors to hepatocytes in vitro and to the liver of mice in vivo. T3 conjugated to the distal ends of fluorescent labeled PEG-g-dextran resulted in T3-specific cellular endosomal uptake into the hepatocellular cell line HepG2. PEG-g-PEI graft copolymers with increasing molar PEG-ratios were synthesized, complexed with plasmid DNA, and transfected into HepG2 or HeLa cells. Gene transfer efficiency decreased as the number of PEG blocks increased. T3 conjugation to PEI and the distal ends of PEG blocks resulted in T3 specific gene transfer in HepG2 cells as evidenced by reduction of gene transfer efficiency after pre-incubation of cells with excess of T3. In vivo application of T3-PEG-g-PEI based gene vectors in mice after tail vein injection resulted in a significantly 7-fold increase of gene expression in the liver compared with PEG-g-PEI based gene vectors. KW - Nonviral KW - PEI KW - Gene transfer KW - Thyroid hormone KW - T3 KW - Liver PY - 2007 SN - 0142-9612 VL - 28 IS - 10 SP - 1900 EP - 1911 PB - Elsevier CY - Oxford AN - OPUS4-14521 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -