TY - CONF A1 - Bleul, Regina A1 - Thiermann, Raphael A1 - Saatchi, K. A1 - Häfeli, U.O. A1 - Maskos, M. ED - Parak, W.J. ED - Osinski, M. ED - Yamamoto, K. T1 - Multifunctional nanocarriers for biomedical applications N2 - 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. T2 - Colloidal nanocrystals for biomedical applications VIII CY - San Francisco, CA, USA DA - 2013-02-22 KW - Polymersomes KW - Vesicles KW - Block copolymers KW - Pluronics KW - Drug delivery KW - Micro mixer PY - 2013 SN - 9780819493644 U6 - https://doi.org/10.1117/12.2008194 N1 - Serientitel: Proceedings of SPIE – Series title: Proceedings of SPIE VL - 8595 SP - 85951N-1 - 85951N-9 AN - OPUS4-28488 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bleul, Regina A1 - Bachran, D. A1 - Thiermann, Raphael A1 - Bertin, Annabelle A1 - Fuchs, H. A1 - Maskos, Michael T1 - Probing polymersome-protein and -cell interactions: influence of different end-groups and environments N2 - 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. KW - Drug delivery KW - End-group functionality KW - Particle-cell interaction KW - Physiologic environment KW - Polymersomes KW - Protein adsorption PY - 2011 U6 - https://doi.org/10.1002/masy.201100042 SN - 1022-1360 SN - 0258-0322 SN - 1521-3900 VL - 309/310 IS - 1 SP - 134 EP - 140 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-25246 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bléger, D. A1 - Liebig, T. A1 - Thiermann, Raphael A1 - Maskos, Michael A1 - Rabe, J.P. A1 - Hecht, S. T1 - Light-orchestrated macromolecular 'accordions': reversible photoinduced shrinking of rigid-rod polymers N2 - 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. N2 - Synthetic molecular systems undergoing structure and property changes as a response to external stimuli offer a series of relevant functions. Their direct use in solution, immobilized at surfaces, or integrated into adequate matrices, allow for the elaboration of nano-carriers, molecular electronic memory circuits, adaptive systems, artificial muscles, or healable materials, among others. Reversible systems are commonly generated by utilizing molecular switches as responsive bi-stable molecules. Of particular interest are switches controlled by non-invasive triggers, especially light, which can display high spatial and temporal resolution. Photoswitches were used to change properties, such as conductance and basicity, based on light-induced alteration of the molecular geometry, that is, their dimensions and shape. In nature, light-induced geometrical modifications of molecular systems lead to primary biological functions, such as the visual perception in vertebrates, or proton pumping in some bacteria, two examples that nicely illustrate the potential of photo-inducing structural modifications in organic systems. KW - Aggregation KW - Azoverbindungen KW - Nanostrukturen KW - Photochromie KW - Polymere PY - 2011 U6 - https://doi.org/10.1002/ange.201106879 SN - 0044-8249 SN - 0932-2140 SN - 1521-3757 VL - 123 IS - 52 SP - 12767 EP - 12771 PB - Wiley-VCH CY - Weinheim AN - OPUS4-25394 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Thiermann, Raphael A1 - Mueller, W. A1 - Montesinos-Castellanos, A. A1 - Metzke, D. A1 - Löb, P. A1 - Hessel, V. A1 - Maskos, Michael T1 - Size controlled polymersomes by continous self-assembly in micromixers N2 - 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. KW - Vesicles KW - Polymersomes KW - Micromixers PY - 2012 U6 - https://doi.org/10.1016/j.polymer.2012.03.058 SN - 0032-3861 SN - 1873-2291 VL - 53 IS - 11 SP - 2205 EP - 2210 PB - Springer CY - Berlin AN - OPUS4-25884 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Waltraut A1 - Koynov, K. A1 - Pierrat, S. A1 - Thiermann, Raphael A1 - Fischer, K. A1 - Maskos, Michael T1 - pH-change protective PB-b-PEO polymersomes N2 - 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. KW - Diblock copolymers KW - Self assembly KW - Vesicle loading PY - 2011 U6 - https://doi.org/10.1016/j.polymer.2011.01.028 SN - 0032-3861 SN - 1873-2291 VL - 52 IS - 5 SP - 1263 EP - 1267 PB - Elsevier Ltd. AN - OPUS4-23520 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Thiermann, Raphael A1 - Maskos, M. T1 - Monodisperse, multifuncional polymersomes in micromixers for biomedical imaging: Continuous synthesis, loading, and self-assembly investigation T2 - ACS National Meeting, Materials for Health and Medicine CY - Philadelphia, PA, USA DA - 2012-08-17 PY - 2012 AN - OPUS4-27314 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Orts Gil, Guillermo A1 - Natte, Kishore A1 - Thiermann, Raphael A1 - Girod, Matthias A1 - Rades, Steffi A1 - Kalbe, Henryk A1 - Thünemann, Andreas A1 - Maskos, M. A1 - Österle, Werner T1 - On the role of surface composition and curvature on biointerface formation and colloidal stability of nanoparticles in a protein-rich model system N2 - 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. KW - Nanoparticles KW - Protein corona KW - Biointerface KW - BSA KW - PEG KW - Colloidal stability PY - 2013 U6 - https://doi.org/10.1016/j.colsurfb.2013.02.027 SN - 0927-7765 SN - 1873-4367 VL - 108 SP - 110 EP - 119 PB - Elsevier B.V. CY - Amsterdam AN - OPUS4-30100 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Koshkina, Olga A1 - Westmeier, D. A1 - Lang, Thomas A1 - Bantz, C. A1 - Hahlbrock, A. A1 - Würth, Christian A1 - Resch-Genger, Ute A1 - Braun, Ulrike A1 - Thiermann, Raphael A1 - Weise, C. A1 - Eravci, M. A1 - Mohr, B. A1 - Schlaad, H. A1 - Stauber, R. H. A1 - Docter, D. A1 - Bertin, Annabelle A1 - Maskos, M. T1 - Tuning the surface of nanoparticles: Impact of poly(2-ethyl-2-oxazoline) on protein adsorption in serum and cellular uptake N2 - 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. KW - Poloxazolines KW - Protein corona KW - Cellular uptake PY - 2016 U6 - https://doi.org/10.1002/mabi.201600074 SN - 1616-5187 SN - 1616-5195 VL - 16 IS - 9 SP - 1287 EP - 1300 AN - OPUS4-37369 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -