TY - JOUR A1 - Kasper, J. A1 - Hermanns, M.I. A1 - Bantz, C. A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Maskos, Michael A1 - Pohl, C. A1 - Unger, R. E. A1 - Kirkpatrick, C.J. T1 - Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins N2 - Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 1006#8211;140 m² displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells (siRNA). This study reveals the relevance of the nanoparticle size regarding cytotoxicity (MTS, LDH) and inflammatory responses (IL-8), whereat the smaller the size of the nanoparticle is, the more harmful are the effects. All different aSNP sizes have been incorporated in flotillin-1- and flotillin-2-labelled vesicles in lung epithelial and endothelial cells, which display a marker for late endosomal or lysosomal structures and appear to exhibit a clathrin- or caveolae-independent mode of endocytosis. Flotillin-depleted H441 showed a clearly decreased uptake of aSNPs. Additionally, the viability of aSNP-exposed cells was reduced in these cells. These findings indicate a contribution of flotillins in as yet unknown (clathrin or caveolae-independent) endocytosis mechanisms and (or) endosomal storage. KW - Silica nanoparticles KW - Alveolar-capillary barrier KW - Lung epithelial cells KW - Endothelial cells KW - Endocytosis KW - Flotillin-1 KW - Flotillin-2 KW - Cytotoxicity KW - Inflammatory response PY - 2012 UR - http://link.springer.com/content/pdf/10.1007%2Fs00204-012-0876-5 U6 - https://doi.org/10.1007/s00204-012-0876-5 SN - 0340-5761 SN - 1432-0738 SP - 1 EP - 13(?) PB - Springer CY - Berlin ; Heidelberg [u.a.] AN - OPUS4-26195 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Lang, Thomas A1 - Bantz, C. A1 - Bertin, Annabelle A1 - Maskos, Michael T1 - Study of protein-nanoparticle interactions with FFF and DLS: Concentration dependency of the aggregation process T2 - SPP1313 Workshop 5: The Nanoparticle-Protein Corona: Characterization, impact and biological relevance CY - Mainz, Germany DA - 2011-12-08 PY - 2011 AN - OPUS4-25168 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Koshkina, Olga A1 - Bantz, C. A1 - Würth, Christian A1 - Lang, Thomas A1 - Resch-Genger, Ute A1 - Maskos, Michael T1 - Fluorophore-labeled siloxane-based nanoparticles for biomedical applications N2 - We present the synthesis and characterization of multifunctional fluorophore-labeled poly(organosiloxane) nanoparticles with core-shell architecture, where the fluorescent dye is incorporated into the core. Grafting of heterobifunctional poly(ethylene oxide) (PEO) onto the particle surface leads to water-soluble biocompatible nanoparticles. Two different strategies have been used for the synthesis: The encapsulation of dye-labeled monomers during the polycondensation with additional PEO coating and subsequent dye labeling by covalent attachment of the fluorescent dye rhodamine B to the (chloromethylphenyl)siloxane groups in the core after polymerization and grafting of PEO onto the surface. Comparison of the fluorescence quantum yields of the nanoparticles before and after PEO coating show a decrease in quantum yield after PEO coating. KW - Biocompatibility KW - Core-shell KW - Fluorescence KW - Fluorescence quantum yield KW - Nanoparticles KW - PEO PY - 2011 U6 - https://doi.org/10.1002/masy.201100041 SN - 1022-1360 SN - 0258-0322 SN - 1521-3900 VL - 309/310 IS - 1 SP - 141 EP - 146 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-25143 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Lang, Thomas A1 - Koshkina, Olga A1 - Maskos, Michael A1 - Bantz, C. T1 - Multifunctional, polymeric nanoparticles in biological environments T2 - 25th European Colloid and Interface Society meeting (ECIS) CY - Berlin, Germany DA - 2011-09-04 PY - 2011 AN - OPUS4-25387 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lang, Thomas A1 - Eslahian, Kyriakos-Alexandros A1 - Maskos, Michael T1 - Ion effects in field-flow fractionation of aqueous colloidal polystyrene N2 - We discuss the effect of electrolytes on retention of aqueous colloidal polystyrene particles in asymmetrical flow (AF-FFF) and thermal field-flow fractionation (ThFFF). In both FFF subtechniques, interparticle interaction leads to non-ideal fractionation behavior, which can result in a sample load dependency. Electrostatic repulsion is reduced with increasing electrolyte concentration, resulting in a pronounced increase of retention. At higher salinities, hydrophobic interactions dominate, thus applications of AF-FFF under physiological conditions are limited. In ThFFF, also the separation mechanism of thermophoresis is affected by ionic shielding and experimental data are in accordance with recent theoretical models of thermophoresis. KW - Asymmetrical flow field-flow fractionation KW - Colloids KW - Interfaces KW - Ion effects KW - Thermal field-flow fractionation PY - 2012 U6 - https://doi.org/10.1002/macp.201200132 SN - 1022-1352 SN - 1521-3935 VL - 213 IS - 22 SP - 2353 EP - 2361 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-27431 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 - TY - JOUR A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Thiermann, R. A1 - Docter, D. A1 - Stauber, R.H. A1 - Secker, C. A1 - Schlaad, H. A1 - Weidner, Steffen A1 - Mohr, B. A1 - Maskos, M. A1 - Bertin, Annabelle T1 - Temperature-triggered protein adsorption on polymer-coated nanoparticles in serum N2 - The protein corona, which forms on the nanoparticle's surface in most biological media, determines the nanoparticle’s physicochemical characteristics. The formation of the protein corona has a significant impact on the biodistribution and clearance of nanoparticles in vivo. Therefore, the ability to influence the formation of the protein corona is essential to most biomedical applications, including drug delivery and imaging. In this study, we investigate the protein adsorption on nanoparticles with a hydrodynamic radius of 30 nm and a coating of thermoresponsive poly(2-isopropyl-2-oxazoline) in serum. Using multiangle dynamic light scattering (DLS) we demonstrate that heating of the nanoparticles above their phase separation temperature induces the formation of agglomerates, with a hydrodynamic radius of 1 µm. In serum, noticeably stronger agglomeration occurs at lower temperatures compared to serum-free conditions. Cryogenic transmission electron microscopy (cryo-TEM) revealed a high packing density of agglomerates when serum was not present. In contrast, in the presence of serum, agglomerated nanoparticles were loosely packed, indicating that proteins are intercalated between them. Moreover, an increase in protein content is observed upon heating, confirming that protein adsorption is induced by the alteration of the surface during phase separation. After cooling and switching the surface back, most of the agglomerates were dissolved and the main fraction returned to the original size of approximately 30 nm as shown by asymmetrical flow-field flow fractionation (AF-FFF) and DLS. Furthermore, the amounts of adsorbed proteins are similar before and after heating the nanoparticles to above their phase-separation temperature. Overall, our results demonstrate that the thermoresponsivity of the polymer coating enables turning the corona formation on nanoparticles on and off in situ. As the local heating of body areas can be easily done in vivo, the thermoresponsive coating could potentially be used to induce the agglomeration of nanoparticles and proteins and the accumulation of nanoparticles in a targeted body region. PY - 2015 U6 - https://doi.org/10.1021/acs.langmuir.5b00537 SN - 0743-7463 SN - 1520-5827 VL - 31 IS - 32 SP - 8873 EP - 8881 PB - American Chemical Society CY - Washington, DC AN - OPUS4-34163 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bantz, C. A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Galla, H.-J. A1 - Kirkpatrick, C.J. A1 - Stauber, R.H. A1 - Maskos, M. T1 - The surface properties of nanoparticles determine the agglomeration state and the size of the particles under physiological conditions N2 - Due to the recent widespread application of nanomaterials to biological systems, a careful consideration of their physiological impact is required. This demands an understanding of the complex processes at the bio–nano interface. Therefore, a comprehensive and accurate characterization of the material under physiological conditions is crucial to correlate the observed biological impact with defined colloidal properties. As promising candidates for biomedical applications, two SiO2-based nanomaterial systems were chosen for extensive size characterization to investigate the agglomeration behavior under physiological conditions. To combine the benefits of different characterization techniques and to compensate for their respective drawbacks, transmission electron microscopy, dynamic light scattering and asymmetric flow field-flow fractionation were applied. The investigated particle systems were (i) negatively charged silica particles and (ii) poly(organosiloxane) particles offering variable surface modification opportunities (positively charged, polymer coated). It is shown that the surface properties primarily determine the agglomeration state of the particles and therefore their effective size, especially under physiological conditions. Thus, the biological identity of a nanomaterial is clearly influenced by differentiating surface properties. KW - Nanomaterial characterization KW - Physiological conditions KW - Surface properties KW - Silica nanoparticles KW - Siloxane nanoparticles KW - Nanoparticles KW - Colloids KW - Silica KW - Polyorganosiloxane KW - Siloxane KW - Characterization KW - Transmission electron microscopy KW - TEM KW - Cryo-TEM KW - Asymetrical flow field-flow fractionation KW - AF-FFF KW - Field-flow fractionation KW - FFF KW - Dynamic light scattering KW - DLS KW - PCS PY - 2014 U6 - https://doi.org/10.3762/bjnano.5.188 SN - 2190-4286 VL - 5 SP - 1774 EP - 1786 CY - Frankfurt, M. AN - OPUS4-32575 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -