TY - CONF A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Maskos, M. A1 - Bantz, C. T1 - Multifunctional, Fluorescently Labeled Polyorgansiloxane-Nanoparticles and their Characterization in Different Biologically Relevant Media T2 - Second Reporting Colloquium of DFG/SPP1313-2 "Bio-Nano-Responses" CY - Fulda, Germany DA - 2013-02-11 PY - 2013 AN - OPUS4-28751 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Schlaad, H. A1 - Kasper, J. A1 - Kirkpatrick, C. J. A1 - Docter, D. A1 - Stauber, R. H. A1 - Hatami, Soheil A1 - Resch-Genger, Ute T1 - Modular Fluorescent Polyorgano(siloxane) Nanoparticles for Biomedical Applications T2 - 245th ACS National Meeting & Exposition CY - New Orleans, LA, USA DA - 2013-04-07 PY - 2013 AN - OPUS4-28753 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - 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 DO - 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 - JOUR A1 - Kasper, J. A1 - Herrmanns, M.I. A1 - Bantz, C. A1 - Utech, S. A1 - Koshkina, Olga A1 - Maskos, Michael A1 - Brochhausen, C. A1 - Pohl, C. A1 - Fuchs, S. A1 - Unger, R. E. A1 - Kirkpatrick, C.J. T1 - Flotillin-involved uptake of silica nanoparticles and responses of an alveolar-capillary barrier in vitro N2 - Drug and gene delivery via nanoparticles across biological barriers such as the alveolar-capillary barrier of the lung constitutes an interesting and increasingly relevant field in nanomedicine. Nevertheless, potential hazardous effects of nanoparticles (NPs) as well as their cellular and systemic fate should be thoroughly examined. Hence, this study was designed to evaluate the effects of amorphous silica NPs (Sicastar) and (poly)organosiloxane NPs (AmOrSil) on the viability and the inflammatory response as well as on the cellular uptake mechanisms and fate in cells of the alveolar barrier. For this purpose, the alveolar epithelial cell line (NCI H441) and microvascular endothelial cell line (ISO-HAS-1) were used in an experimental set up resembling the alveolar-capillary barrier of the lung. In terms of IL-8 and sICAM Sicastar resulted in harmful effects at higher concentrations (60 µg/ml) in conventional monocultures but not in the coculture, whereas AmOrSil showed no significant effects. Immunofluorescence counterstaining of endosomal structures in NP-incubated cells showed no evidence for a clathrin- or caveolae-mediated uptake mechanism. However, NPs were enclosed in flotillin-1 and -2 marked vesicles in both cell types. Flotillins appear to play a role in cellular uptake or trafficking mechanisms of NPs and are discussed as indicators for clathrin- or caveolae-independent uptake mechanisms. In addition, we examined the transport of NPs across this in vitro model of the alveolar-capillary barrier forming a tight barrier with a transepithelial electrical resistance of 560 ± 8 Ω cm². H441 in coculture with endothelial cells took up much less NPs compared to monocultures. Moreover, coculturing prevented the transport of NP from the epithelial compartment to the endothelial layer on the bottom of the filter insert. This supports the relevance of coculture models, which favour a differentiated and polarised epithelial layer as in vitro test systems for nanoparticle uptake. KW - Silica nanoparticles KW - Alveolar-capillary barrier KW - NP uptake KW - NP-transport KW - Endocytosis KW - Flotillin-1/-2-dependent uptake/trafficking PY - 2013 DO - https://doi.org/10.1016/j.ejpb.2012.10.011 SN - 0939-6411 SN - 1873-3441 VL - 84 IS - 2 SP - 275 EP - 287 PB - Elsevier B.V. CY - Amsterdam AN - OPUS4-28841 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Bantz, C. A1 - Lang, Thomas A1 - Kasper, J. A1 - Kirkpatrick, C. J. A1 - Würth, Christian A1 - Resch-Genger, Ute A1 - Maskos, Michael T1 - Fluorescent Poly(organosiloxane) Nanoparticles in Biological Environment T2 - SPP1313 Workshop 5: The Nanoparticle-Protein Corona: Characterization, impact and biological relevance CY - Mainz, Germany DA - 2011-12-08 PY - 2011 AN - OPUS4-25169 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 DO - 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 - Koshkina, Olga A1 - Lang, Thomas A1 - Schlaad, H. A1 - Docter, D. A1 - Stauber, R. H. A1 - Harishandra, R. A1 - Galla, H.-J. A1 - Hatami, Soheil A1 - Resch-Genger, Ute T1 - Siloxane Based Nanoparticles in Biological Environment T2 - Young Scientist Workshop, IMM CY - Mainz, Germany DA - 2013-09-19 PY - 2013 AN - OPUS4-29617 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Schlaad, H. A1 - Kasper, J. A1 - Kirkpatrick, C. J. A1 - Docter, D. A1 - Hatami, Soheil A1 - Resch-Genger, Ute A1 - Bantz, C. T1 - Modular Fluorescent Poly(organosiloxane) Nanoparticles for Biomedical Applications T2 - IUPAC 10th International Conference on Advanced Polymers via Macromolecular Engineering CY - Durham, England DA - 2013-08-18 PY - 2013 AN - OPUS4-29618 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Bleul, Regina A1 - Bantz, C. A1 - Maskos, Michael T1 - Fluorescent Dye-labeled polyorganosiloxane nanospheres for biomedical applications T2 - 7th International Conference on Biomedical Applications of Nanotechnology CY - Berlin, Germany DA - 2010-12-02 PY - 2010 AN - OPUS4-22717 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Lang, Thomas A1 - Bantz, C. A1 - Maskos, M. T1 - Synthesis and Characterization of Siloxane-Based Nanoparticles for Biomedical Applications T2 - First Reporting Colloquium of DFG SPP1313-2 "Bio-Nano-Responses" CY - Fulda, Germany DA - 2012-02-20 PY - 2012 AN - OPUS4-25471 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Bantz, C. A1 - Kasper, J. A1 - Kirkpatrick, C. J. A1 - Docter, D. A1 - Stauber, R. H. A1 - Hatami, Soheil A1 - Resch-Genger, Ute A1 - Maskos, M. T1 - Multifunctional Fluorescent Poly(organosiloxane) Nanoparticles; Synthesis and Characterization in Biological Environments by Dynamic Light Scattering T2 - Polydays 2012 CY - Berlin, Germany DA - 2012-09-30 PY - 2012 AN - OPUS4-27316 LA - deu 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 DO - 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 - Dwivedi, M.V. A1 - Harishchandra, R.K. A1 - Koshkina, Olga A1 - Maskos, M. A1 - Galla, H.-J. T1 - Size influences the effect of hydrophobic nanoparticles on lung surfactant model systems N2 - The alveolar lung surfactant (LS) is a complex lipid protein mixture that forms an interfacial monolayer reducing the surface tension to near zero values and thus preventing the lungs from collapse. Due to the expanding field of nanotechnology and the corresponding unavoidable exposure of human beings from the air, it is crucial to study the potential effects of nanoparticles (NPs) on the structural organization of the lung surfactant system. In the present study, we investigated both, the domain structure in pure DPPC monolayers as well as in lung surfactant model systems. In the pure lipid system we found that two different sized hydrophobic polymeric nanoparticles with diameter of ~12 nm and ~136 nm have contrasting effect on the functional and structural behavior. The small nanoparticles inserted into fluid domains at the LE-LC phase transition are not visibly disturbing the phase transition but disrupting the domain morphology of the LE phase. The large nanoparticles led to an expanded isotherm and to a significant decrease in the line tension and thus to a drastic disruption of the domain structures at a much lower number of nanoparticles with respect to the lipid. The surface activity of the model LS films again showed drastic variations due to presence of different sized NPs illustrated by the film balance isotherms and the atomic force microscopy. AFM revealed laterally profuse multilayer protrusion formation on compression but only in the presence of 136 nm sized nanoparticles. Moreover we investigated the vesicle insertion process into a preformed monolayer. A severe inhibition was observed only in the presence of ~136 nm NPs compared to minor effects in the presence of ~12 nm NPs. Our study clearly shows that the size of the nanoparticles made of the same material determines the interaction with biological membranes. KW - Lung surfactant KW - Nanoparticle size KW - Surface activity KW - Atomic force microscopy KW - Vesicle insertion kinetics KW - Multilayer protrusion structures PY - 2014 DO - https://doi.org/10.1016/j.bpj.2013.10.036 SN - 0006-3495 SN - 1542-0086 VL - 106 IS - 1 SP - 289 EP - 298 PB - Biophysical Society CY - Bethesda, Md. AN - OPUS4-30519 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Bantz, C. A1 - Lang, Thomas A1 - Würth, Christian A1 - Resch-Genger, Ute A1 - Maskos, Michael T1 - Synthesis and Characterisation of Siloxane Based Nanoparticles for in Vitro studies T2 - Advanced Functional Polymers for Medicine 2011 CY - Enschede, Netherlands DA - 2011-06-15 PY - 2011 AN - OPUS4-23896 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Koshkina, Olga A1 - Bleul, Regina A1 - Bantz, C. A1 - Maskos, Michael T1 - Fluorescent Dye-labeled Polyorganosiloxane Nanospheres for Biomedical Applications T2 - Polydays 2010 CY - Berlin, Germany DA - 2010-10-03 PY - 2010 AN - OPUS4-22147 LA - deu 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 DO - 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 DO - 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 -