TY - JOUR A1 - Orts Gil, Guillermo A1 - Natte, Kishore A1 - Drescher, Daniela A1 - Bresch, Harald A1 - Mantion, Alexandre A1 - Kneipp, J. A1 - Österle, Werner T1 - Characterisation of silica nanoparticles prior to in vitro studies: from primary particles to agglomerates N2 - The size, surface charge and agglomeration state of nanoparticles under physiological conditions are fundamental parameters to be determined prior to their application in toxicological studies. Although silica-based materials are among the most promising candidates for biomedical applications, more systematic studies concerning the characterisation before performing toxicological studies are necessary. This interest is based on the necessity to elucidate the mechanisms affecting its toxicity. We present here TEM, SAXS and SMPS as a combination of methods allowing an accurate determination of single nanoparticle sizes. For the commercial material, Ludox TM50 single particle sizes around 30 nm were found in solution. DLS measurements of single particles are rather affected by polydispersity and particles concentration but this technique is useful to monitor their agglomeration state. Here, the influence of nanoparticle concentration, ionic strength (IS), pH and bath sonication on the agglomeration behaviour of silica particles in solution has been systematically investigated. Moreover, the colloidal stability of silica particles in the presence of BSA has been investigated showing a correlation between silica and protein concentrations and the formation of agglomerates. Finally, the colloidal stability of silica particles in standard cell culture medium has been tested, concluding the necessity of surface modification in order to preserve silica as primary particles in the presence of serum. The results presented here have major implications on toxicity investigations because silica agglomeration will change the probability and uptake mechanisms and thereby may affect toxicity. KW - Silica KW - Toxicology KW - Agglomeration KW - BSA KW - Nanoparticles KW - Characterisation PY - 2011 U6 - https://doi.org/10.1007/s11051-010-9910-9 SN - 1388-0764 SN - 1572-896X VL - 13 IS - 4 SP - 1593 EP - 1604 PB - Springer AN - OPUS4-21179 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Drescher, Daniela A1 - Orts Gil, Guillermo A1 - Laube, G. A1 - Natte, Kishore A1 - Veh, R.W. A1 - Österle, Werner A1 - Kneipp, Janina T1 - Toxicity of amorphous silica nanoparticles on eukaryotic cell model is determined by particle agglomeration and serum protein adsorption effects N2 - Cell cultures form the basis of most biological assays conducted to assess the cytotoxicity of nanomaterials. Since the molecular environment of nanoparticles exerts influence on their physicochemical properties, it can have an impact on nanotoxicity. Here, toxicity of silica nanoparticles upon delivery by fluid-phase uptake is studied in a 3T3 fibroblast cell line. Based on XTT viability assay, cytotoxicity is shown to be a function of (1) particle concentration and (2) of fetal calf serum (FCS) content in the cell culture medium. Application of dynamic light scattering shows that both parameters affect particle agglomeration. The DLS Experiments verify the stability of the nanoparticles in culture medium without FCS over a wide range of particle concentrations. The related toxicity can be mainly accounted for by single silica nanoparticles and small agglomerates. In contrast, agglomeration of silica nanoparticles in all FCS-containing media is observed, resulting in a decrease of the associated toxicity. This result has implications for the evaluation of the cytotoxic potential of silica nanoparticles and possibly also other nanomaterials in standard cell culture. KW - Agglomeration KW - Cytotoxicity KW - Fibroblast cells KW - Serum proteins KW - Silica nanoparticles PY - 2011 U6 - https://doi.org/10.1007/s00216-011-4893-7 SN - 1618-2642 SN - 1618-2650 VL - 400 IS - 5 SP - 1367 EP - 1373 PB - Springer CY - Berlin AN - OPUS4-23678 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Natte, Kishore A1 - Behnke, Thomas A1 - Orts Gil, Guillermo A1 - Würth, Christian A1 - Friedrich, Jörg Florian A1 - Österle, Werner A1 - Resch-Genger, Ute T1 - Synthesis and characterisation of highly fluorescent core-shell nanoparticles based on Alexa dyes N2 - Current and future developments in the emerging field of nanobiotechnology are closely linked to the rational design of novel fluorescent nanomaterials, e.g. for biosensing and imaging applications. Here, the synthesis of bright near infrared (NIR)-emissive nanoparticles based on the grafting of silica nanoparticles (SNPs) with 3-aminopropyl triethoxysilane (APTES) followed by covalent attachment of Alexa dyes and their subsequent shielding by an additional silica shell are presented. These nanoparticles were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM) and fluorescence spectroscopy. TEM studies revealed the monodispersity of the initially prepared and fluorophorelabelled silica particles and the subsequent formation of raspberry-like structures after addition of a silica precursor.Measurements of absolute fluorescence quantum yields of these scattering particle suspensions with an integrating sphere setup demonstrated the influence of dye labelling density-dependent fluorophore aggregation on the signaling behaviour of such nanoparticles. KW - Silica KW - Alexa dyes KW - Fluorescent particles KW - Quantum yields KW - Nanoparticles KW - Protective shell KW - Nanobiotechnology PY - 2012 U6 - https://doi.org/10.1007/s11051-011-0680-9 SN - 1388-0764 SN - 1572-896X VL - 14 IS - 2 SP - 680-1 - 680-10 PB - Kluwer CY - Dordrecht AN - OPUS4-25872 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Natte, Kishore A1 - Österle, Werner A1 - Friedrich, Jörg Florian A1 - von Klitzing, R. A1 - Orts-Gil, Guillermo T1 - Tuning interfacial properties and colloidal behavior of hybrid nanoparticles by controlling the polymer precursor N2 - A facile and versatile synthetic route for controlling the size and surface potential of organic–inorganic hybrid silica nanoparticles (NPs) is introduced in this paper. For polymer-grafted NPs, the density of polymer chains on the surface is strongly affected by the concentration of precursor. Nevertheless, for condensed NPs, the precursor concentration determines the particle size but not the density of polymer chains on the surface or the adsorption of bovine serum albumin (BSA). Results presented here may have Major implications in biomedical and colloidal chemistry since interfacial and colloidal properties are known to drive several processes associated with nanoparticles in biological media. KW - BSA KW - Bio-interface KW - Nanosilica hybrids KW - PEG KW - Protein corona PY - 2012 U6 - https://doi.org/10.1002/macp.201200148 SN - 0025-116X SN - 1022-1352 SN - 1521-3935 VL - 213 IS - 22 SP - 2412 EP - 2419 PB - Whiley-VCH CY - Weinheim AN - OPUS4-38549 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Orts Gil, Guillermo A1 - Natte, Kishore A1 - Österle, Werner T1 - Multi-parametric reference nanomaterials for toxicology: state of the art, future challenges and potential candidates N2 - A major requirement for the validation of methods assessing the risk associated with engineered nanoparticles (ENPs) is the use of reference materials (RMs). In the present contribution we review available RMs, ongoing projects and characterisation trends in the field. The conclusion is that actual approaches to RMs mostly deal with metrological considerations about single properties of the ENPs, typically their primary size, which can hardly be representative of nanoparticles characteristics in real testing media and therefore, not valid for reliable and comparable toxicological studies. As an alternative, we discussed the convenience and feasibility of establishing multi-parametric RMs for a series of ENPs, focusing on silica nanoparticles (SNPs). As a future perspective, the need to develop RMs based on hybrid nanoparticles is also discussed. KW - Referenzmaterialien KW - Nanopartikel KW - Toxikologie KW - Metrologie PY - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:b43-292997 SN - 2046-2069 VL - 3 IS - 40 SP - 18202 EP - 18215 PB - RSC Publishing CY - London AN - OPUS4-29299 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Natte, Kishore A1 - Friedrich, Jörg Florian A1 - Wohlrab, Sebastian A1 - Lutzki, J. A1 - von Klitzing, R. A1 - Österle, Werner A1 - Orts-Gil, Guillermo T1 - Impact of polymer shell on the formation and time evolution of nanoparticle-protein corona N2 - The study of protein corona formation on nanoparticles (NPs) represents an actual main issue in colloidal, biomedical and toxicological sciences. However, little is known about the influence of polymer shells on the formation and time evolution of protein corona onto functionalized NPs. Therefore, silicapoly(ethylene glycol) core–shell nanohybrids (SNPs@PEG) with different polymer molecular weights (MW) were synthesized and exhaustively characterized. Bovine serum albumin (BSA) at different concentrations (0.1–6 wt%) was used as model protein to study protein corona formation and time evolution. For pristine SNPs and SNPs@PEG (MW = 350 g/mol), zeta potential at different incubation times show a dynamical evolution of the nanoparticle–protein corona. Oppositely, for SNPs@PEG with MW ≥2000 g/mol a significant suppression of corona formation and time evolution was observed. Furthermore, AFM investigations suggest a different orientation (side-chain or perpendicular) and Penetration depth of BSA toward PEGylated surfaces depending on the polymer length which may explain differences in protein corona evolution. KW - Nanoparticles KW - Silica KW - PEGylation KW - Protein corona KW - BSA KW - Biointerface PY - 2013 U6 - https://doi.org/10.1016/j.colsurfb.2012.11.019 SN - 0927-7765 VL - 104 SP - 213 EP - 220 PB - Elsevier AN - OPUS4-38547 LA - eng 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 -