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 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 - Hennig, C. A1 - Takao, S. A1 - Takao, K. A1 - Weiss, s. A1 - Kraus, Werner A1 - Emmerling, Franziska A1 - Meyer, M. A1 - Scheinost, A.C. T1 - Identification of hexanuclear actinide(IV) carboxylates with thorium, uranium and neptunium by EXAFS spectroscopy N2 - Hydrated actinide(IV) ions undergo hydrolysis and further polymerization and precipitation with increasing pH. The resulting amorphous and partly crystalline oxydydroxides AnOn(OH)4-2n·xH2O can usually be observed as colloids above the An(IV) solubility limit. The aging process of such colloids results in crystalline AnO2. The presence of carboxylates in the solution prevents the occurrence of such colloids by formation of polynuclear complexes through a competing reaction between hydrolysis and ligation. The majority of recently described carboxylates reveals a hexanuclear core of [An6(µ3-O)4(µ3-OH)4]12+ terminated by 12 carboxylate ligands. We found that the An(IV) carboxylate solution species remain often preserved in crystalline state. The An(IV) carboxylates show An–An distances which are ~ 0.03 Å shorter than the An–An distances in AnO2 like colloids. The difference in the distances could be used to identify such species in solution. T2 - XAFS15 - 15th International conference on X-ray absorption fine structure CY - Beijing, China DA - 22.07.2012 KW - Carboxylates KW - EXAFS KW - Actinide PY - 2013 DO - https://doi.org/10.1088/1742-6596/430/1/012116 SN - 1742-6588 SN - 1742-6596 VL - 430 SP - 012116-1 EP - 012116-5 PB - IOP Publ. CY - Bristol, UK AN - OPUS4-28525 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -