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Author: Hoeppener, Stephanie × Type: Text ×

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Now showing 1 - 6 of 6
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    Stealth Effect of Short Polyoxazolines in Graft Copolymers: Minor Changes of Backbone End Group Determine Liver Cell-Type Specificity
    (Washington, DC : ACS Publications, 2021) Muljajew, Irina; Huschke, Sophie; Ramoji, Anuradha; Cseresnyés, Zoltán; Hoeppener, Stephanie; Nischang, Ivo; Foo, Wanling; Popp, Jürgen; Figge, Marc Thilo; Weber, Christine; Bauer, Michael; Schubert, Ulrich S.; Press, Adrian T.
    Dye-loaded micelles of 10 nm diameter formed from amphiphilic graft copolymers composed of a hydrophobic poly(methyl methacrylate) backbone and hydrophilic poly(2-ethyl-2-oxazoline) side chains with a degree of polymerization of 15 were investigated concerning their cellular interaction and uptake in vitro as well as their interaction with local and circulating cells of the reticuloendothelial system in the liver by intravital microscopy. Despite the high molar mass of the individual macromolecules (Mn ≈ 20 kg mol-1), backbone end group modification by attachment of a hydrophilic anionic fluorescent probe strongly affected the in vivo performance. To understand these effects, the end group was additionally modified by the attachment of four methacrylic acid repeating units. Although various micelles appeared similar in dynamic light scattering and cryo-transmission electron microscopy, changes in the micelles were evident from principal component analysis of the Raman spectra. Whereas an efficient stealth effect was found for micelles formed from polymers with anionically charged or thiol end groups, a hydrophobic end group altered the micelles' structure sufficiently to adapt cell-type specificity and stealth properties in the liver. © 2021 The Authors. Published by American Chemical Society.
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    Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis
    (Heidelberg : EMBO Press, 2021) Press, Adrian T.; Babic, Petra; Hoffmann, Bianca; Müller, Tina; Foo, Wanling; Hauswald, Walter; Benecke, Jovana; Beretta, Martina; Cseresnyés, Zoltán; Hoeppener, Stephanie; Nischang, Ivo; Coldewey, Sina M.; Gräler, Markus H.; Bauer, Reinhard; Gonnert, Falk; Gaßler, Nikolaus; Wetzker, Reinhard; Figge, Marc Thilo; Schubert, Ulrich S.; Bauer, Michael
    Jaundice, the clinical hallmark of infection-associated liver dysfunction, reflects altered membrane organization of the canalicular pole of hepatocytes and portends poor outcomes. Mice lacking phosphoinositide 3-kinase-γ (PI3Kγ) are protected against membrane disintegration and hepatic excretory dysfunction. However, they exhibit a severe immune defect that hinders neutrophil recruitment to sites of infection. To exploit the therapeutic potential of PI3Kγ inhibition in sepsis, a targeted approach to deliver drugs to hepatic parenchymal cells without compromising other cells, in particular immune cells, seems warranted. Here, we demonstrate that nanocarriers functionalized through DY-635, a fluorescent polymethine dye, and a ligand of organic anion transporters can selectively deliver therapeutics to hepatic parenchymal cells. Applying this strategy to a murine model of sepsis, we observed the PI3Kγ-dependent restoration of biliary canalicular architecture, maintained excretory liver function, and improved survival without impairing host defense mechanisms. This strategy carries the potential to expand targeted nanomedicines to disease entities with systemic inflammation and concomitantly impaired barrier functionality.
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    Microwave-Assisted Synthesis of Core–Shell Nanoparticles—Insights into the Growth of Different Geometries
    (Weinheim : Wiley-VCH, 2020) Womiloju, Aisha A.; Höppener, Christiane; Schubert, Ulrich S.; Hoeppener, Stephanie
    Microwave irradiation is utilized for the rapid synthesis of gold–silver core–shell bimetallic nanoparticles (NPs) in a two-step process. A strategy of establishing a bilayer organic barrier around the core using citrate and ascorbic acid as capping agents, providing a means to achieve a well-defined boundary layer between the core and the shell material, is reported. These boundary layers are essential for synthesizing different core–shell morphologies and the approach results in tunable bimetallic NPs with defined core–shell structures, both for spherical as well as for triangular seed cores. In addition, theoretical calculations of the plasmonic characteristics based on the boundary element method of different classes of NPs are conducted. These investigations enable conclusions to be drawn on the influence of the core morphology on the tunability of their localized surface plasmon resonances. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Tuning the corona-core ratio of polyplex micelles for selective oligonucleotide delivery to hepatocytes or hepatic immune cells
    (Amsterdam [u.a.] : Elsevier Science, 2023) Foo, WanLing; Cseresnyés, Zoltán; Rössel, Carsten; Teng, Yingfeng; Ramoji, Anuradha; Chi, Mingzhe; Hauswald, Walter; Huschke, Sophie; Hoeppener, Stephanie; Popp, Jürgen; Schacher, Felix H.; Sierka, Marek; Figge, Marc Thilo; Press, Adrian T.; Bauer, Michael
    Targeted delivery of oligonucleotides or small molecular drugs to hepatocytes, the liver's parenchymal cells, is challenging without targeting moiety due to the highly efficient mononuclear phagocyte system (MPS) of the liver. The MPS comprises Kupffer cells and specialized sinusoidal endothelial cells, efficiently clearing nanocarriers regardless of their size and surface properties. Physiologically, this non-parenchymal shield protects hepatocytes; however, these local barriers must be overcome for drug delivery. Nanocarrier structural properties strongly influence tissue penetration, in vivo pharmacokinetics, and biodistribution profile. Here we demonstrate the in vivo biodistribution of polyplex micelles formed by polyion complexation of short interfering (si)RNA with modified poly(ethylene glycol)-block-poly(allyl glycidyl ether) (PEG-b-PAGE) diblock copolymer that carries amino moieties in the side chain. The ratio between PEG corona and siRNA complexed PAGE core of polyplex micelles was chemically varied by altering the degree of polymerization of PAGE. Applying Raman-spectroscopy and dynamic in silico modeling on the polyplex micelles, we determined the corona-core ratio (CCR) and visualized the possible micellar structure with varying CCR. The results for this model system reveal that polyplex micelles with higher CCR, i.e., better PEG coverage, exclusively accumulate and thus allow passive cell-type-specific targeting towards hepatocytes, overcoming the macrophage-rich reticuloendothelial barrier of the liver.
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    On the stability of microwave-fabricated SERS substrates - chemical and morphological considerations
    (Frankfurt, M. : Beilstein-Institut zur Förderung der Chemischen Wissenschaften, 2021) Wang, Limin; Womiloju, Aisha Adebola; Höppener, Christiane; Schubert, Ulrich Sigmar; Hoeppener, Stephanie
    The stability of surface-enhanced Raman spectroscopy (SERS) substrates in different organic solvents and different buffer solutions was investigated. SERS substrates were fabricated by a microwave-assisted synthesis approach and the morphological as well as chemical changes of the SERS substrates were studied. It was demonstrated that the SERS substrates treated with methanol, ethanol, or N,N-dimethylformamide (DMF) were comparable and showed overall good stability and did not show severe morphological changes or a strong decrease in their Raman activity. Toluene treatment resulted in a strong decrease in the Raman activity whereas dimethyl sulfoxide (DMSO) treatment completely preserved or even slightly improved the Raman enhancement capabilities. SERS substrates immersed into phosphate-buffered saline (PBS) solutions were observed to be rather instable in low and neutral pH buffer solutions. Other buffer systems showed less severe influences on the SERS activity of the substrates and a carbonate buffer at pH 10 was found to even improve SERS performance. This study represents a guideline on the stability of microwave-fabricated SERS substrates or other SERS substrates consisting of non-stabilized silver nanoparticles for the application of different organic solvents and buffer solutions.
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    Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2023) Quansah, Elsie; Gardey, Elena; Ramoji, Anuradha; Meyer-Zedler, Tobias; Goehrig, Bianca; Heutelbeck, Astrid; Hoeppener, Stephanie; Schmitt, Michael; Waldner, Maximillian; Stallmach, Andreas; Popp, Jürgen
    The intestinal epithelial barrier, among other compartments such as the mucosal immune system, contributes to the maintenance of intestinal homeostasis. Therefore, any disturbance within the epithelial layer could lead to intestinal permeability and promote mucosal inflammation. Considering that disintegration of the intestinal epithelial barrier is a key element in the etiology of ulcerative colitis, further assessment of barrier integrity could contribute to a better understanding of the role of epithelial barrier defects in ulcerative colitis (UC), one major form of chronic inflammatory bowel disease. Herein, we employ fast, non-destructive, and label-free non-linear methods, namely coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon fluorescence lifetime imaging (2P-FLIM), to assess the morpho-chemical contributions leading to the dysfunction of the epithelial barrier. For the first time, the formation of epithelial barrier gaps was directly visualized, without sophisticated data analysis procedures, by the 3D analysis of the colonic mucosa from severely inflamed UC patients. The results were compared with histopathological and immunofluorescence images and validated using transmission electron microscopy (TEM) to indicate structural alterations of the apical junction complex as the underlying cause for the formation of the epithelial barrier gaps. Our findings suggest the potential advantage of non-linear multimodal imaging is to give precise, detailed, and direct visualization of the epithelial barrier in the gastrointestinal tract, which can be combined with a fiber probe for future endomicroscopy measurements during real-time in vivo imaging.