Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-28488 Beitrag zu einem Tagungsband Bleul, Regina; Thiermann, Raphael; Saatchi, K.; Häfeli, U.O.; Maskos, M. Parak, W.J.; Osinski, M.; Yamamoto, K. Multifunctional nanocarriers for biomedical applications Polymeric vesicles (Pluronic® L-121) loaded with magnetic nanoparticles (MNP) and an anti-cancer drug (camptothecin) were prepared continuously in a micro mixing device. Characterization by TEM confirmed the successful incorporation of the MNP and DLS measurements showed a relatively narrow size distribution of the hybrid polymersomes. A very high drug loading of camptothecin (100 µg/ml in the polymersome formulation) was reached and a drug release study of loaded magnetic polymersomes has shown a sustained camptothecin release over several days. Carboxylation of Pluronic® L-121 was performed and enabled a further surface functionalization with bombesin, a 14 amino acid peptide, which binds specifically to the GRPR (gastrin releasing peptide receptor). This receptor is often overexpressed in tumor cells (e.g., human prostate cancer cells) and therefore a suitable target for cancer treatment. An additional fluorescence label with Alexa Fluor® 647 allow tracking of the polymersomes e.g., in cell experiments. Relaxivity measurements to evaluate the potential of magnetic polymersomes as MR contrast agent for in vivo imaging are in progress. Society of photo-optical instrumentation engineers (SPIE) 2013 Colloidal nanocrystals for biomedical applications VIII (Proceedings of SPIE) 8595 9780819493644 Colloidal nanocrystals for biomedical applications VIII San Francisco, CA, USA 2013-02-22 2013-02-22 85951N-1 - 85951N-9 10.1117/12.2008194 2016-02-20 OPUS4-25246 Zeitschriftenartikel Bleul, Regina; Bachran, D.; Thiermann, Raphael; Bertin, Annabelle; Fuchs, H.; Maskos, Michael Probing polymersome-protein and -cell interactions: influence of different end-groups and environments Developing polymersomes for drug delivery purposes requires a deeper understanding of their behavior in physiological environment. We performed the self-assembly and in-situ loading of polybutadiene-block-polyethyleneoxide (PB-b-PEO) polymersomes in a continuous process using micromixers. Varying the length and end-groups of the starting block copolymer allows us to control the polymer membrane thickness and surface functionalities (hydroxyl or carboxylic acid), required to realize a further coupling with specific cell targeting ligands. To get a deeper understanding of these polymersomes in physiological environment, we studied the cellular response (HeLa cells) in presence of various polymersomes, and showed by cytotoxicity tests the relative biocompatibility of the systems. Flow cytometry experiments at 4?°C in PBS buffer showed a different behavior of hydroxyl-functionalized vesicles compared to carboxylic acid-functionalized vesicles. On the contrary cell binding in DMEM medium supplemented with 10% FCS was almost completely blocked with both kinds of polymersomes. Protein adsorption measurements by dynamic light scattering confirmed that protein binding occurs in all cases, which apparently influences the particle-cell interaction. This study contributes towards a deeper understanding of polymersomes in biological environment and further investigations will help us to design highly effective polymersomes for in vitro as well as in vivo applications. Weinheim Wiley-VCH Verl. 2011 Macromolecular symposia 309/310 1 134 140 10.1002/masy.201100042 2016-02-19 OPUS4-25394 Zeitschriftenartikel Bléger, D.; Liebig, T.; Thiermann, Raphael; Maskos, Michael; Rabe, J.P.; Hecht, S. Light-orchestrated macromolecular 'accordions': reversible photoinduced shrinking of rigid-rod polymers Lichtspiele: Lichteinstrahlung verursacht drastische Änderungen der Form stabförmiger Polymere mit Azobenzol-Photochromen in der Hauptkette. Die eingebetteten Photoschalter wirken als molekulare Scharniere, die bei lichtinduzierter Isomerisierung zur reversiblen Schrumpfung und Streckung des Polymerrückgrats führen (siehe Schema); das System erinnert an ein lichtorchestriertes makromolekulares Akkordeon. Weinheim Wiley-VCH Gesellschaft Deutscher Chemiker 2011 Angewandte Chemie 123 52 12767 12771 10.1002/ange.201106879 2016-02-19 OPUS4-25884 Zeitschriftenartikel Thiermann, Raphael; Mueller, W.; Montesinos-Castellanos, A.; Metzke, D.; Löb, P.; Hessel, V.; Maskos, Michael Size controlled polymersomes by continous self-assembly in micromixers The formation of vesicles based on the self-assembly of amphiphilic poly(butadiene)-b-poly(ethylene oxide) (PB130-b-PEO66) block copolymer in water has been studied using THF as co-solvent. To obtain a highly controlled mixing process for the polymer/THF- and the water-phase, we employed micro mixers with different mixing geometries. The high impact of this preparation method on the self-assembling process was verified by TEM and DLS characterization of the obtained structures. Spherical micelles, vesicles and worm-like micelles were found depending on the parameters of mixing. By additional parameter adjustment in the vesicle regime, the size of the assembled vesicles was controlled between 45 and 100 nm. This demonstrates the continuous preparation of narrowly distributed vesicle structures with controlled sizes. Berlin Springer 2012 Polymer 53 11 2205 2210 10.1016/j.polymer.2012.03.058 2016-02-19 OPUS4-23520 Zeitschriftenartikel Müller, Waltraut; Koynov, K.; Pierrat, S.; Thiermann, Raphael; Fischer, K.; Maskos, Michael pH-change protective PB-b-PEO polymersomes Poly(butadiene)-b-poly(ethylene oxide) vesicles were successfully loaded with hydrophilic dye Phloxine B. Dye addition during vesicle formation leads to Phloxine B encapsulated inside the water filled vesicle core as well as to freely diffusing dye molecules. The removal of uncapsulated substrate involves time consuming methods like dialysis or harsher methods like ultra filtration or selective precipitation, posing the risk of irreversible sample manipulation. Here used Phloxine B as pH sensitive fluorescence indicator allows the characterization of hydrophilic loading without separation procedure by adjusting the pH value. Additionally membrane blocking efficiency can be studied by time dependent fluorescence measurements. Cryogenic TEM studies showed that the self-assembled structure remained unchanged when the hydrophilic dye was incorporated within the vesicles. Fluorescence microscopy imaging proved the encapsulation of the hydrophilic dye inside the core volume. The combination of fluorescence correlation spectroscopy (FCS) and dynamic light scattering (DLS) measurements as ensemble methods confirmed those results additionally. Elsevier Ltd. 2011 Polymer 52 5 1263 1267 10.1016/j.polymer.2011.01.028 2016-02-19 OPUS4-27314 Vortrag Thiermann, Raphael Monodisperse, multifuncional polymersomes in micromixers for biomedical imaging: Continuous synthesis, loading, and self-assembly investigation 2012 ACS National Meeting, Materials for Health and Medicine ACS National Meeting, Materials for Health and Medicine Philadelphia, PA, USA 2012-08-17 2012-08-21 2016-02-20 OPUS4-30100 Zeitschriftenartikel Orts Gil, Guillermo; Natte, Kishore; Thiermann, Raphael; Girod, Matthias; Rades, Steffi; Kalbe, Henryk; Thünemann, Andreas; Maskos, M.; Österle, Werner On the role of surface composition and curvature on biointerface formation and colloidal stability of nanoparticles in a protein-rich model system The need for a better understanding of nanoparticle–protein interactions and the mechanisms governing the resulting colloidal stability has been emphasised in recent years. In the present contribution, the short and long term colloidal stability of silica nanoparticles (SNPs) and silica-poly(ethylene glycol) nanohybrids (Sil-PEG) have been scrutinised in a protein model system. Well-defined silica nanoparticles are rapidly covered by bovine serum albumin (BSA) and form small clusters after 20 min while large agglomerates are detected after 10 h depending on both particle size and nanoparticle-protein ratio. Oppositely, Sil-PEG hybrids present suppressive protein adsorption and enhanced short and long term colloidal stability in protein solution. No critical agglomeration was found for either system in the absence of protein, proving that instability found for SNPs must arise as a consequence of protein adsorption and not to high ionic environment. Analysis of the small angle X-ray scattering (SAXS) structure factor indicates a short-range attractive potential between particles in the silica-BSA system, which is in good agreement with a protein bridging agglomeration mechanism. The results presented here point out the importance of the nanoparticle surface properties on the ability to adsorb proteins and how the induced or depressed adsorption may potentially drive the resulting colloidal stability. Amsterdam Elsevier B.V. 2013 Colloids and surfaces B: Biointerfaces 108 110 119 10.1016/j.colsurfb.2013.02.027 2016-02-20 OPUS4-37369 Zeitschriftenartikel Koshkina, Olga; Westmeier, D.; Lang, Thomas; Bantz, C.; Hahlbrock, A.; Würth, Christian; Resch-Genger, Ute; Braun, Ulrike; Thiermann, Raphael; Weise, C.; Eravci, M.; Mohr, B.; Schlaad, H.; Stauber, R. H.; Docter, D.; Bertin, Annabelle; Maskos, M. Tuning the surface of nanoparticles: Impact of poly(2-ethyl-2-oxazoline) on protein adsorption in serum and cellular uptake Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles. 2016 Macromolecular Bioscience 16 9 1287 1300 10.1002/mabi.201600074 2016-09-15